MedPath

Chimpanzee Adenovirus and Self-Amplifying mRNA Prime-Boost Prophylactic Vaccines Against SARS-CoV-2 in Healthy Adults

Phase 1
Completed
Conditions
COVID-19
Interventions
Other: Sodium Chloride, 0.9%
Registration Number
NCT04776317
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

This is a multicenter, US-only, phase 1, open-label, dose escalation, non-randomized study of the safety, tolerability, and immunogenicity of investigational ChAd and SAM SARS-CoV-2 vaccines in healthy adult subjects. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 EUA/licensed vaccines (Stage 2) will be examined. Subjects' willingness to receive ChAd vaccines will be assessed and documented at the time of informed consent and considered to determine group assignments. This phase 1 study will enroll 17 Stage 1 and up to 118 Stage 2 subjects. Eligible subjects will be enrolled in different groups based on their age (18-60 years old and \>60 years old) and their EUA/licensed COVID-19 vaccination status. A sentinel approach with 72-hour (Stage 1, and Stage 2, Groups 5, 6, 8-10, 12, 13-15) or 7-day observation times (Groups 7 and 11) will be used, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC with consultation with the DSMB as needed after all subjects in each group have been observed through Day 8 post first study vaccination. All subjects will be followed through 12 months after their last study vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. Escalation to the highest dose (10 µg) of SAM-S-TCE in younger subjects will proceed only following safety assessments of the 10 µg dose in older subjects for a period of 28 days post-vaccination. In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with the Johnson \& Johnson/Janssen Ad26 COVID-19 EUA/licensed vaccine in Groups 8A, 8B, and 12A, 12B will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively. After protocol version 9.0 was implemented, it was decided not to enroll subjects into Groups 7 and 8 because of competing priorities and predicted difficulties enrolling into these two groups.

The primary objectives of this study are 1) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as prime-boost in healthy naïve adult subjects, 2) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as first or second boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA/licensed vaccine.

Detailed Description

This is a multicenter, US-only, phase 1, open-label, dose escalation, non-randomized study of the safety, tolerability, and immunogenicity of investigational ChAd and SAM SARS-CoV-2 vaccines in healthy adult subjects. Homologous and heterologous prime-boost vaccination schedules (Stage 1), as well as boost(s) after receipt of COVID-19 EUA/licensed vaccines (Stage 2) will be examined. Subjects' willingness to receive ChAd vaccines will be assessed and documented at the time of informed consent and considered to determine group assignments. This phase 1 study will enroll 17 Stage 1 and up to 118 Stage 2 subjects. Eligible subjects will be enrolled in different groups based on their age (18-60 years old and \>60 years old) and their EUA/licensed COVID-19 vaccination status. A sentinel approach with 72-hour (Stage 1, and Stage 2, Groups 5, 6, 8-10, 12, 13-15) or 7-day observation times (Groups 7 and 11) will be used, before recruiting the remainder of each dose escalation group. Decisions about dose escalation will be determined by the SSC with consultation with the DSMB as needed after all subjects in each group have been observed through Day 8 post first study vaccination. All subjects will be followed through 12 months after their last study vaccination. Vaccinated subjects will be carefully monitored for exposure and infection to SARS-CoV-2 throughout the study. Escalation to the highest dose (10 µg) of SAM-S-TCE in younger subjects will proceed only following safety assessments of the 10 µg dose in older subjects for a period of 28 days post-vaccination. In addition, the dosage of SAM-S-TCE given as a double boost to subjects previously vaccinated with the Johnson \& Johnson/Janssen Ad26 COVID-19 EUA/licensed vaccine in Groups 8A, 8B, and 12A, 12B will be determined based on the dose escalation reactogenicity and immunogenicity results in Groups 5-7 and 9-11, respectively. After protocol version 9.0 was implemented, it was decided not to enroll subjects into Groups 7 and 8 because of competing priorities and predicted difficulties enrolling into these two groups.

The primary objectives of this study are 1) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as prime-boost in healthy naïve adult subjects, 2) To assess the safety and tolerability of different doses of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE when administered as first or second boost in healthy adult subjects previously vaccinated with an mRNA or adenoviral-vectored COVID-19 EUA/licensed vaccine. The secondary objective of this study is to assess the humoral immunogenicity of ChAd-S or ChAd-S-TCE, and SAM-S or SAM-S-TCE.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
81
Inclusion Criteria

Subjects eligible to participate in this trial must meet all of the following inclusion criteria:

  1. Provide written informed consent prior to initiation of any study procedures

  2. Able and willing (in the investigator's opinion) to comply with all study requirements

  3. Are men or non-pregnant women aged 18 years or older at enrollment

  4. Are in good health*

    *As defined by absence of clinically significant medical conditions defined by the CDC as increasing risk for severe corona virus disease-19 (COVID-19) (see exclusion criteria), or other acute or chronic medical conditions determined by medical history, physical examination (PE), screening laboratory test results, and/or clinical assessment of the investigator that are either listed as exclusion criteria below or in the opinion of the investigator would increase risk for study participation or affect the assessment of the safety of subjects. Chronic medical conditions should be stable for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedures). Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site PI or appropriate sub- investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes in the 60 days prior to enrollment as well as subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination.

  5. Agree to refrain from blood donation during the course of the study

  6. Plan to remain living in the area for the duration of the study

  7. Women of childbearing potential (WOCBP)* must plan to avoid pregnancy for at least 60 days after the last study vaccination and be willing to use an adequate method of contraception** consistently for 30 days prior to first study vaccine and for at least 60 days after the last study vaccine.

    *Not sterilized via bilateral oophorectomy, tubal ligation/salpingectomy, hysterectomy, or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization with documented radiological confirmation test at least 90 days after the procedure); still menstruating; or < 1 year has passed since the last menses if menopausal

    **Acceptable methods of birth control include the following: oral contraceptives, injection hormonal contraceptive, implant hormonal contraceptive, hormonal patch, intrauterine device, spermicidal products and barrier methods (such as cervical sponge, diaphragm, or condom with spermicide), abstinence, monogamous with a vasectomized partner, non-male sexual relationship

  8. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each study vaccination

  9. Vital signs within acceptable ranges:

    • Pulse > 50 and = / < 100 beats per minute
    • Systolic blood pressure (BP) = / < 140 millimeters of mercury (mmHg)
    • Diastolic BP = / < 90 mmHg
    • Oral temperature < 37.8 degrees Celsius (100.0 degrees Fahrenheit)

  10. Clinical screening lab evaluations (white blood cell (WBC), hemoglobin (HgB), platelets (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (T Bili), creatine kinase (CK), serum creatinine (Cr) and prothrombin time (PT)/partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical lab being used* *With the exception that ALT, AST, ALP, and creatinine values that are below the reference range will not be exclusionary as these values below reference range are clinically insignificant. Any other screening lab value outside the reference range that is thought to be clinically insignificant by a site investigator must be discussed with the DMID Medical Officer prior to enrollment.

  11. Must agree to genetic testing and storage of samples for secondary research

  12. Received at least 2 doses of EUA/licensed mRNA vaccines or at least 1 dose of Ad26 vaccine followed by an mRNA booster, with the last COVID-19 vaccine dose given at least 112 days prior to enrollment (Stage 2 only), as confirmed via CDC vaccination card or other appropriate documentation. Subjects may or may not have been previously infected with SARS-CoV-2.

A subject must meet all of the following criteria to be eligible for leukapheresis:

  1. Written informed consent for leukapheresis is provided
  2. Weight > / = 110 pounds
  3. Screening laboratory evaluations are within acceptable ranges at the site where the leukapheresis procedure will be performed
  4. Negative urine or serum pregnancy test at screening and on the day of the leukapheresis procedure for women of childbearing potential
  5. Adequate bilateral antecubital venous access
  6. No use of blood thinners, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) at least 5 days before the leukapheresis procedure
Exclusion Criteria

Subjects eligible to participate in this trial must not meet any of the following exclusion criteria:

  1. History of prior confirmed (PCR or antigen test positive) COVID-19 less than 112 days prior to enrollment.

  2. Positive for anti-nucleoprotein SARS-CoV-2 specific antibody by enzyme-linked immunosorbent assay (ELISA) and had the history of upper respiratory illness (URI) compatible with COVID-19 during the 112 days prior to enrollment (seropositivity without a history of URI during the 112 days prior to enrollment will be considered remotely infected persons eligible for enrollment).

  3. Positive nasal swab polymerase chain reaction (PCR) at screening.

  4. Body mass index (BMI) > 30 kg/m^2 for Stage 1 participants and BMI > 35 kg/m^2 for Stage 2 participants.

  5. Presence of medical comorbidities that would place the subject at increased risk for severe COVID-19*

    *Chronic kidney disease, chronic lung disease (including moderate-to-severe asthma), chronic heart disease (heart failure, coronary artery disease or cardiomyopathies), cerebrovascular disease, diabetes mellitus, chronic liver disease, sickle cell disease

  6. Increased risk of occupational exposure to SARS-CoV-2 (healthcare workers and emergency response personnel)*

    *Applies to Stage 1 participants only

  7. Prior receipt of an approved/licensed or investigational SARS-CoV-2 vaccine (including under EUA)*, approved or investigational adenovirus-vectored vaccines**, or any other approved or investigational vaccine likely to impact the interpretation of the trial data.

    *Exclusion of prior receipt of EUA/licensed COVID-19 vaccines applies to Stage 1 participants only.

    **With the exception of prior receipt of EUA/licensed Johnson & Johnson/Janssen Ad 26 COVID-19 vaccine which is permitted for Groups 8A, 8B, 12A, and 12B.

  8. On current treatment or prevention agents with activity against SARS-CoV-2

  9. Current smoking or vaping or history of smoking or vaping in prior year*

    *Applies to Stage 1 participants only

  10. Breastfeeding, pregnant, or planning to become pregnant during the course of the study.

  11. Participation in another research study involving receipt of an investigational product in the 60 days preceding enrolment or planned use during the study period

  12. Receipt or planned receipt of any live, attenuated vaccine within 28 days before or after study vaccination

  13. Receipt or planned receipt of any subunit or killed vaccine within 14 days before or after vaccination

  14. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of first study vaccination or at any time during the study

  15. Any confirmed or suspected immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection, asplenia, recurrent, severe infections and chronic (more than 14 continuous days) immunosuppressant medication within the past 6 months (inhaled, ophthalmic, and topical steroids are allowed)

  16. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain (or any immediate allergic reaction of any severity to polysorbate due to potential cross-reactive hypersensitivity with the polyethylene glycol component of the vaccine)

  17. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema

  18. Any history of anaphylaxis, including but not limited to reaction to vaccination

  19. Any history of severe allergic drug reaction

  20. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)

  21. History of serious ongoing, unstable psychiatric condition that in the opinion of the investigator would interfere with study participation

  22. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years

  23. Bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture or family history of bleeding disorder

  24. Recent (within the past 3 months) surgery, immobility, chronic infection, or head trauma that could increase the risks of thrombosis.

  25. Suspected or known current alcohol abuse. Suspected or known drug abuse in the 5 years preceding enrollment

  26. Seropositive for HIV, hepatitis B surface antigen (HBsAg), or seropositive for hepatitis C virus (antibodies to HCV)

  27. Have an acute illness* within 72 hours prior to study vaccination

    *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol

  28. History of venous or arterial thrombosis or any known thrombophilic condition including heparin-induced thrombocytopenia (HIT) or family history of thrombosis.

  29. History of myocarditis or pericarditis.

  30. History of Guillain-Barre Syndrome (GBS).

  31. Receiving heparin treatment or on medications associated with increased risk of bleeding or thrombosis.

  32. Any other condition that in the opinion of the investigator would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Stage 1 (Naïve) Group 3ASodium Chloride, 0.9%30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=3
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 9Sodium Chloride, 0.9%3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=8
Stage 1 (Naïve) Group 1ChAdV68-S5 x 10\^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=4
Stage 1 (Naïve) Group 3BSodium Chloride, 0.9%30 mcg SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-LNP-S administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=7
Stage 1 (Naïve) Group 4Sodium Chloride, 0.9%10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=3
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 14Sodium Chloride, 0.9%1 x 10\^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=7-10
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 6Sodium Chloride, 0.9%6 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. N=10
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 13ChAdV68-S-TCE5 x 10\^10 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and on or after Day 113 in participants older than 60 years of age. N=7-10
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 13Sodium Chloride, 0.9%5 x 10\^10 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and on or after Day 113 in participants older than 60 years of age. N=7-10
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 5Sodium Chloride, 0.9%3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. N=10
Stage 1 (Naïve) Group 1Sodium Chloride, 0.9%5 x 10\^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=4
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 14ChAdV68-S-TCE1 x 10\^11 viral particles of ChAdV68-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=7-10
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 10A,BSAM-LNP-S-TCE6 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=8-12
Stage 1 (Naïve) Group 3BSAM-LNP-S30 mcg SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-LNP-S administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=7
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 15Sodium Chloride, 0.9%5 x 10\^11 viral particles of ChAdV68-S-TCE administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=7-10
Stage 1 (Naïve) Group 3ASAM-LNP-S30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=3
Stage 1 (Naïve) Group 1SAM-LNP-S5 x 10\^10 viral particles of ChAdV68-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 30 mcg of SAM-LNP-S administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 29 in participants from 18 to 60 years of age. N=4
Stage 1 (Naïve) Group 4SAM-LNP-S-TCE10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on or after Day 85 and no later than Day 130 in participants from 18 to 60 years of age. N=3
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 6SAM-LNP-S-TCE6 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. N=10
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 8A,BSAM-LNP-S-TCE10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 57 in participants from 18 to 60 years of age. N=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 11A,BSAM-LNP-S-TCE10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 12A,BSAM-LNP-S-TCE10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 and 10 mcg SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 57 in participants older than 60 years of age. N=8-12
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 5SAM-LNP-S-TCE3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. N=10
Stage 2 (SAM-S-TCE Boosts after EUA/licensed mRNA COVID-19 Vaccines) Group 7A,BSAM-LNP-S-TCE10 mcg of SAM-S-TCE administered through 0.5 mL intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 60 years of age. N=8-12
Stage 2 (SAM-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 9SAM-LNP-S-TCE3 mcg of SAM-S-TCE administered through 0.25 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=8
Stage 2 (ChAd-S-TCE Boosts after approved/licensed mRNA COVID-19 Vaccines) Group 15ChAdV68-S-TCE5 x 10\^11 viral particles of ChAdV68-S-TCE administered through 1.0 mL intramuscular injection in the deltoid muscle on Day 1 in participants older than 60 years of age. N=7-10
Primary Outcome Measures
NameTimeMethod
Frequency of Any New-onset Chronic Medical Conditions (NOCMCs)Day 1 to study completion through up to 1 year post last dose

Number of participants that experienced any NOCMCs during the course of the study

Frequency of Any Potentially Immune-mediated Medical Conditions (PIMMCs)Day 1 to study completion through up to 1 year post last dose

Number of participants that experienced any PIMMCs during the course of the study

Frequency of Any Medically Attended Adverse Events (MAAEs)Day 1 to study completion through up to 1 year post last dose

Number of participants that experienced any MAAEs during the course of the study

Frequency of Any Laboratory AEThrough 7 days post each study vaccination

Number of participants that experienced any laboratory AE

Frequency of Any Serious Adverse Events (SAEs)Day 1 to study completion through up to 1 year post last dose

The number of participants that experience any SAEs from Day 1 to study completion. An AE or suspected adverse reaction is considered serious if, in the view of either the participating site PI or appropriate sub-investigator or the sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and through 7 days post any vaccination for Groups 1, 3A, 3b and 4.

Number of participants who experienced any systemic solicited AEs through 7 days post any vaccination. Systemic events include: fatigue, headache, myalgia, arthralgia, nausea, chills and fever.

Frequency of Local Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and through 7 days post any vaccination for Groups 1, 3A, 3b and 4.

Number of participants who experienced any local solicited AEs through 7 days post any vaccination. Local events include: pain at injection site, erythema, and induration.

Frequency of Any Unsolicited Adverse Events (AEs)Day 1 through Day 29 for Groups 5, 6, 9, 10, 11, 13, 14 and 15 and 28 days post any vaccination for Groups 1, 3A, 3b and 4.

Number of participants who experienced any unsolicited AEs through 28 days post vaccination

Secondary Outcome Measures
NameTimeMethod
Mean Percent of CD4+ T Cells With G-Nuc Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-Nuc stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-ORFa Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-ORFa stimulation expressing IFNg and/or IL-2

Geometric Mean Titer of RBD IgG as Measured by ELISA for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of RBD titer

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.1 for Groups 1 and 3ADay 57 Post Vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against D614G for Groups 1 and 3ADay 29 Post Vaccination 1, Day 57 Post Vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 1 and 3ADay 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against D614G for Groups 3B and 4Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.1 for Groups 3B and 4Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 3B and 4Day 169 Post Vac 1 (85 Days Post Vac 2), Day 265 Post Vac 1 (181 Days Post Vac 2), Day 450 Post Vac 1 (366 Days Post Vac 2)

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination 1 titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against D614G for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.1 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination titer.

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean Fold Rise of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5. Fold-rise is calculated by dividing post-vaccination titers by the Day 1 Pre-Vaccination titer.

Geometric Mean of Pseudovirus Neutralization ID50 Against D614G for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.1 for Groups 1 and 3ADay 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 1 and 3ADay 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5

Geometric Mean of Pseudovirus Neutralization ID50 Against D614G for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.1 for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 3B and 4Day 169 Post Vaccination 1 (85 Days Post Vaccination 2), Day 265 Post Vaccination 1 (181 Days Post Vaccination 2), Day 450 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5

Geometric Mean of Pseudovirus Neutralization ID50 Against D614G for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.1 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1

Geometric Mean of Pseudovirus Neutralization ID50 Against BA.4/5 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean of Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5

Geometric Mean Titer of RBD IgG as Measured by ELISA for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean of RBD titer

Geometric Mean in Titer of RBD IgG as Measured by ELISA for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean of RBD titer

Geometric Mean Titer of S-2P IgG as Measured by ELISA for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Geometric Mean of S-2P titer

Geometric Mean Titer of S-2P IgG as Measured by ELISA for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Geometric Mean of S-2P titer

Geometric Mean in Titer of S-2P IgG as Measured by ELISA for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Geometric Mean of S-2P titer

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against D614G S-2P for Groups 1 and 3ADay 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.1 S-2P for Groups 1 and 3ADay 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.1 S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.4/5 S-2P for Groups 1 and 3ADay 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against BA.4/5 S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against D614G S-2P for Groups 3B and 4Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution) against D614G S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.1 S-2P for Groups 3B and 4Day 29 Post Vaccination 1, Day 57 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1, Day 450 Post Vaccination 1

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution), against BA.1 S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.4/5 S-2P for Groups 3B and 4Day 169 Post Vaccination 1 (85 Days Post Vaccination 2), Day 265 Post Vaccination 1 (181 Days Post Vaccination 2), Day 450 Post Vaccination 1 (366 Days Post Vaccination 2)

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution), against BA.4/5 S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against D614G S-2P for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution), against D614G S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.1 S-2P for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution), against BA.1 S-2P

Percent of Participants Who Seroconverted Based on Pseudovirus Neutralization ID50 Against BA.4/5 S-2P for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 15 Post Vaccination, Day 29 Post Vaccination, Day 85 Post Vaccination, Day 181 Post Vaccination, Day 366 Post Vaccination

Percent of Participants Who Seroconverted, defined as a 4-fold change in Pseudovirus Neutralization ID50 (50% Inhibitory Dilution), against BA.4/5 S-2P

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 1 and 3ADay 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 1 and 3ADay 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With Any TCE Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any TCE stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With Any TCE Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with Any TCE stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-Mem Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-Mem stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With G-Mem Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-Mem stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-Nuc Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-Nuc stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With G-Nuc Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-Nuc stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-ORFa Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-ORFa stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With G-ORFa Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Mean Percent of CD4+ T Cells with G-ORFa stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With Any TCE Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with Any TCE stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With Any TCE Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with Any TCE stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-Mem Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-Mem stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With G-Mem Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-Mem stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Mean Percent of CD4+ T Cells With G-Nuc Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-Nuc stimulation expressing IFNg and/or IL-2

Mean Percent of CD4+ T Cells With G-ORFa Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Mean Percent of CD4+ T Cells with G-ORFa stimulation expressing IL-4 or IL-5 or IL-13 and CD154

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 1 and 3ADay 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 1 and 3ADay 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Mean T-cells Expressing IL-13 in pg/mL for Groups 3B and 4 at Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)

Mean T-cells Expressing IL-13 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing TNF-alpha in pg/mL for Groups 3B and 4 at Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)

Mean T-cells Expressing TNF-alpha in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-2 in pg/mL for Groups 5 and 6 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-2 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-4 in pg/mL for Groups 5 and 6 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-4 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-10 in pg/mL for Groups 5 and 6 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-10 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-13 in pg/mL for Groups 5 and 6 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-13 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing TNF-alpha in pg/mL for Groups 5 and 6 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing TNF-alpha in pg/mL as measured by MSD cytokine assay

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any TCE Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any TCE stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any TCE Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with Any TCE stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Mem Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-Mem stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Mem Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-Mem stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Nuc Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-Nuc stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Nuc Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-Nuc stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-ORFa Stimulation Expressing IFNg and/or IL-2 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-ORFa stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-ORFa Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 3B and 4Day 1 Pre-Vaccination, Day 29 Post Vaccination 1, Day 85 Post Vaccination 1, Day 99 Post vaccination 1 (15 Days Post Vaccination 2)

Percent of Responders: CD4+ T Cells with G-ORFa stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any COV2 S Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with Any COV2 S stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any TCE Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with Any TCE stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With Any TCE Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with Any TCE stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Mem Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-Mem stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Mem Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-Mem stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Nuc Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-Nuc stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-Nuc Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-Nuc stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-ORFa Stimulation Expressing IFNg and/or IL-2 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-ORFa stimulation expressing IFNg and/or IL-2.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-values using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Percent of Responders: CD4+ T Cells With G-ORFa Stimulation Expressing IL-4 or IL-5 or IL-13 and CD154 for Groups 5, 6, 9, 10, 11, 13, 14 and 15Day 1 Pre-Vaccination, Day 15 Post Vaccination

Percent of Responders: CD4+ T Cells with G-ORFa stimulation expressing IL-4 or IL-5 or IL-13 and CD154.

To assess positivity for a peptide pool within a T cell subset, a two-by-two contingency table was constructed comparing the stimulated and negative control data. The four entries in each table were the number of cells positive for the cytokine of interest and the number of cells negative for the cytokine, for both the stimulated and the negative control data. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the individual peptide pool p-vals using the Bonferroni-Holm adjustment method. If the adjusted p-val for a peptide pool was =0.00001, the response to the peptide pool for the T cell subset was considered positive.

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Membrane Frame for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the 15mer OLPs Spanning Membrane Frame as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPa Spanning Nucleocapsid Frame for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the 15mer OLPa Spanning Nucleocapsid Frame as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Open Reading Frame 3a for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the 15mer OLPs spanning Open Reading Frame 3a as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 1st of 4 OLP Pools for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 1st of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 2nd of 4 OLP Pools for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 2nd of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 3rd of 4 OLP Pools for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 3rd of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 4th of 4 OLP Pools for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 4th of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the S1 for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the S1 as measured by ELISpot

Mean Spot Forming Units Per Million of the S2 for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the S2 as measured by ELISpot

Mean T-cells Expressing IL-2 in pg/mL for Groups 3B and 4 at Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)

Mean T-cells Expressing IL-2 in pg/mL as measured by MSD cytokine assay

Mean Spot Forming Units Per Million of the Spike for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the Spike as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLP (Overlapping Peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a for Groups 1 and 3ADay 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1 (29 Days Post Vaccination 2), Day 209 Post Vaccination 1 (181 Days Post Vaccination 2), Day 394 Post Vaccination 1 (366 Days Post Vaccination 2)

Mean spot forming units per million of the 15mer OLP (overlapping peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Membrane Frame for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPs Spanning Membrane Frame as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPa Spanning Nucleocapsid Frame for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPa Spanning Nucleocapsid Frame as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Open Reading Frame 3a for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPs spanning Open Reading Frame 3a as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 1st of 4 OLP Pools for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 1st of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 2nd of 4 OLP Pools for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 2nd of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 3rd of 4 OLP Pools for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 3rd of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 4th of 4 OLP Pools for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 4th of 4 OLP pools as measured by ELISpot

Mean Spot Forming Units Per Million of the S1 for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the S1 as measured by ELISpot

Mean Spot Forming Units Per Million of the S2 for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the S2 as measured by ELISpot

Mean Spot Forming Units Per Million of the Spike for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the Spike as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLP (Overlapping Peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a for Groups 3B and 4Day 1 Pre-Vaccination 1, Day 29 Post Vaccination 1, Day 57 Post vaccination 1, Day 85 Post Vaccination 1, Day 99 Post Vaccination 1, Day 113 Post Vaccination 1, Day 169 Post Vaccination 1, Day 265 Post Vaccination 1

Mean spot forming units per million of the 15mer OLP (overlapping peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a as measured by ELISpot

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Membrane Frame for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPs Spanning Membrane Frame as measured by ELISpot.

Mean Spot Forming Units Per Million of the 15mer OLPa Spanning Nucleocapsid Frame for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPa Spanning Nucleocapsid Frame as measured by ELISpot.

Mean Spot Forming Units Per Million of the 15mer OLPs Spanning Open Reading Frame 3a for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the 15mer OLPs spanning Open Reading Frame 3a as measured by ELISpot.

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 1st of 4 OLP Pools for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 1st of 4 OLP pools as measured by ELISpot.

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 2nd of 4 OLP Pools for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 2nd of 4 OLP pools as measured by ELISpot.

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 3rd of 4 OLP Pools for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 3rd of 4 OLP pools as measured by ELISpot.

Mean Spot Forming Units Per Million of the Consensus Spike (Wuhan-1) Whole Protein, 4th of 4 OLP Pools for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the Consensus Spike (Wuhan-1) whole protein, 4th of 4 OLP pools as measured by ELISpot.

Mean Spot Forming Units Per Million of the S1 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the S1 as measured by ELISpot.

Mean Spot Forming Units Per Million of the S2 for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the S2 as measured by ELISpot.

Mean Spot Forming Units Per Million of the Spike for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the Spike as measured by ELISpot.

Mean Spot Forming Units Per Million of the 15mer OLP (Overlapping Peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a for Groups 5, 6, 9, 10, 11, 13, 14, and 15Day 1 Pre-Vaccination 1, Day 15 Post Vaccination 1, Day 29 Post vaccination 1, Day 85 Post Vaccination 1, Day 181 Post Vaccination 1

Mean spot forming units per million of the 15mer OLP (overlapping peptides) Spanning Membrane, Nucleocapsid, and Open Reading Frame 3a as measured by ELISpot.

Mean T-cells Expressing IL-2 in pg/mL for Groups 1 and 3A at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-2 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-4 in pg/mL for Groups 1 and 3A at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-4 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-10 in pg/mL for Groups 1 and 3A at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-10 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-13 in pg/mL for Groups 1 and 3A at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-13 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing TNF-alpha in pg/mL for Groups 1 and 3A at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing TNF-alpha in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-2 in pg/mL for Groups 3B and 4 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-2 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-4 in pg/mL for Groups 3B and 4 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-4 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-10 in pg/mL for Groups 3B and 4 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-10 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-13 in pg/mL for Groups 3B and 4 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing IL-13 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing TNF-alpha in pg/mL for Groups 3B and 4 at Day 29 Post Vaccination 1Day 29 Post Vaccination 1

Mean T-cells Expressing TNF-alpha in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-4 in pg/mL for Groups 3B and 4 at Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)

Mean T-cells Expressing IL-4 in pg/mL as measured by MSD cytokine assay

Mean T-cells Expressing IL-10 in pg/mL for Groups 3B and 4 at Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)Day 113 Post Vaccination 1 (29 Days Post Vaccination 2)

Mean T-cells Expressing IL-10 in pg/mL as measured by MSD cytokine assay

Trial Locations

Locations (4)

The Hope Clinic of Emory University

🇺🇸

Decatur, Georgia, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Saint Louis University Center for Vaccine Development

🇺🇸

Saint Louis, Missouri, United States

The University of Washington - Virology Research Clinic

🇺🇸

Seattle, Washington, United States

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