MedPath

Safety and Immunogenicity of Clade C ALVAC and gp120 HIV Vaccine

Phase 1
Completed
Conditions
HIV Infections
Interventions
Biological: ALVAC-HIV (vCP2438)
Biological: Bivalent Subtype C gp120
Biological: Bivalent Subtype C gp120/MF59
Biological: Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension
Registration Number
NCT03284710
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

The purpose of this study is to evaluate the safety and immune response to an HIV clade C vaccine and to an MF59- or alum-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.

Detailed Description

This study will evaluate the safety, tolerability, and immunogenicity to vCP2438 (an HIV clade C vaccine) and to an unadjuvanted or MF59- or alum-adjuvanted bivalent clade C gp120 in healthy, HIV-uninfected adults.

The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants will be randomly assigned to one of 4 groups. \[describe further\]

Study visits will include a physical examination, an interview and/or questionnaire, HIV testing and HIV risk-reduction counseling, and urine and blood collection. A subset of participants will provide rectal fluid, cervical fluid, semen, or stool samples.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
132
Inclusion Criteria

General and Demographic Criteria

  1. Age of 18 to 40 years

  2. Access to a participating HVTN CRS and willingness to be followed for the planned duration of the study

  3. Ability and willingness to provide informed consent

  4. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly

  5. Agrees not to enroll in another study of an investigational research agent

  6. Good general health as shown by medical history, physical exam, and screening laboratory tests

    HIV-Related Criteria:

  7. Willingness to receive HIV test results

  8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling.

  9. Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit.

    Laboratory Inclusion Values

    Hemogram/Complete blood count (CBC)

  10. Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers who were born male

  11. White blood cell count = 3,300 to 12,000 cells/mm^3

  12. Total lymphocyte count ≥ 800 cells/mm^3

  13. Remaining differential either within institutional normal range or with site physician approval

  14. Platelets = 125,000 to 550,000/mm^3

    Chemistry

  15. Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of normal; creatinine ≤ institutional upper limit of normal.

    Virology

  16. Negative HIV-1 and -2 blood test: Sites may use locally available assays that have been approved by HVTN Laboratory Operations.

  17. Negative Hepatitis B surface antigen (HBsAg)

  18. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase chain reaction (PCR) if the anti-HCV is positive Urine

  19. Normal urine:

    • Negative urine glucose, and
    • Negative or trace urine protein, and
    • Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis with red blood cells levels within institutional normal range).

    Reproductive Status

  20. Volunteers who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of initial vaccination. Persons who are NOT of reproductive potential due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing.

  21. Reproductive status: A volunteer who was born female must:

    • Agree to consistently use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using condoms (male or female), or diaphragm or cervical cap, PLUS 1 of the following methods: Intrauterine device (IUD), Hormonal contraception (in accordance with Republic of South Africa: National Contraception Clinical Guidelines), successful vasectomy in the male partner (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy); or any other contraceptive method approved by the HVTN 107 Protocol Safety Review Team
    • Or not be of reproductive potential, such as having reached menopause (no menses for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;
    • Or be sexually abstinent.

  22. Volunteers who were born female must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

    Other

  23. Volunteers who were born female consenting to provide cervical samples: pap smear within the 3 years prior to enrollment, with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance); for those 21 years and older that have not had a pap smear within the last 3 years prior to enrollment, must be willing to undergo a pap smear with the result reported as normal or ASCUS prior to sample collection.

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Exclusion Criteria

General

  1. Blood products received within 120 days before first vaccination

  2. Investigational research agents received within 30 days before first vaccination

  3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known hyperlipidemia

  4. Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 107 study

  5. Pregnant or breastfeeding

    Vaccines and other Injections

  6. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 107 PSRT will determine eligibility on a case-by-case basis.

  7. Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure in a volunteer's country of residence. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 107 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by the HVTN 107 PSRT on a case-by-case basis.

  8. Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

  9. Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B)

  10. Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination

    Immune System

  11. Immunosuppressive medications received within 168 days before first vaccination. (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and length of therapy < 11 days with completion at least 30 days prior to enrollment.)

  12. Serious adverse reactions to vaccines or to vaccine components such as eggs, egg products, or neomycin, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded from participation: a volunteer who had a nonanaphylactic adverse reaction to pertussis vaccine as a child.)

  13. Immunoglobulin received within 60 days before first vaccination

  14. Autoimmune disease

  15. Immunodeficiency

    Clinically significant medical conditions

  16. Untreated or incompletely treated syphilis infection

  17. Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

    • A process that would affect the immune response,
    • A process that would require medication that affects the immune response,
    • Any contraindication to repeated injections or blood draws,
    • A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,
    • A condition or process for which signs or symptoms could be confused with reactions to vaccine, or
    • Any condition specifically listed among the exclusion criteria below.

  18. Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a volunteer's ability to give informed consent

  19. Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

  20. Current anti-tuberculosis (TB) prophylaxis or therapy

  21. Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report).

    Exclude a volunteer who:

    • Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

    • Uses moderate/high dose inhaled corticosteroids, or

    • In the past year has either of the following:

      • Greater than 1 exacerbation of symptoms treated with oral/parenteral corticosteroids;
      • Needed emergency care, urgent care, hospitalization, or intubation for asthma.

  22. Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not excluded: history of isolated gestational diabetes.)

  23. Thyroidectomy, or thyroid disease requiring medication during the last 12 months

  24. Hypertension:

    • If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at enrollment.
    • If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.

  25. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions)

  26. Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure. or who is unlikely to experience recurrence of malignancy during the period of the study)

  27. Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.

  28. Asplenia: any condition resulting in the absence of a functional spleen

  29. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 4: ALVAC-HIV + gp120Bivalent Subtype C gp120Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Group 3: ALVAC-HIV + gp120/MF59Bivalent Subtype C gp120/MF59Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid and Bivalent Subtype C gp120/MF59 in the right deltoid at months 0, 1, 6, and 12. All injections are via needle and syringe.
Group 1: ALVAC-HIV + gp120/MF59Bivalent Subtype C gp120/MF59Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120/MF59 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Group 2: ALVAC-HIV + gp120/Al(OH)3ALVAC-HIV (vCP2438)Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Group 2: ALVAC-HIV + gp120/Al(OH)3Bivalent Subtype C gp120 admixed with Al(OH)3 SuspensionParticipants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 admixed with Al(OH)3 Suspension in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Group 1: ALVAC-HIV + gp120/MF59ALVAC-HIV (vCP2438)Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120/MF59 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Group 3: ALVAC-HIV + gp120/MF59ALVAC-HIV (vCP2438)Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid and Bivalent Subtype C gp120/MF59 in the right deltoid at months 0, 1, 6, and 12. All injections are via needle and syringe.
Group 4: ALVAC-HIV + gp120ALVAC-HIV (vCP2438)Participants will receive the ALVAC-HIV (vCP2438) vaccine in the left deltoid at months 0, 1, 3, 6, and 12, and Bivalent Subtype C gp120 in the right deltoid at months 3, 6, and 12. All injections are via needle and syringe.
Primary Outcome Measures
NameTimeMethod
Occurrence of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3Measured at Month 6.5

Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or TendernessMeasured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

Number of Participants Reporting Serious Adverse Events (SAEs)Measured through Month 18

Measured as outlined in Version 2.0 (January 2010) of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual).

Chemistry and Hematology Laboratory Measures - ALT (SGPT), AST, Alkaline PhosphataseMeasured during screening, Days 7, 42, 98, 182, 378, and 455

For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

Level of Vaccine-induced Serum IgA Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 3Measured at Month 6.5

Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Comparisons were performed among positive responders only (positivity criteria are described in Outcome 1).

Number of Participants Reporting Adverse Events (AEs), by Severity GradeMeasured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12

For participants reporting multiple AEs over the time frame, the maximum severity grade is counted.

Chemistry and Hematology Laboratory Measures - CreatinineMeasured during screening, Days 7, 42, 98, 182, 378, and 455

For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

Chemistry and Hematology Laboratory Measures - HemoglobinMeasured during screening, Days 7, 42, 98, 182, 378, and 455

For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

Chemistry and Hematology Laboratory Measures - Lymphocytes, NeutrophilsMeasured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455

For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

Occurrence of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2Measured at Month 6.5

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

Level of Vaccine-induced Systemic IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C) in Group 1 and Group 2Measured at Month 6.5

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Comparisons were performed among positive responders only (positivity criteria are described in Outcome 1).

Number of Participants Reporting Systemic Reactogenicity Signs and SymptomsMeasured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.

Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or IndurationMeasured through Month Measured through 3 days after each vaccine dose at Months 0, 1, 3, 6, and 12

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.

Number of Participants Reporting Adverse Events (AEs), by Relationship to Study ProductMeasured through 30 days after each vaccine dose at Months 0, 1, 3, 6, and 12

For participants reporting multiple AEs over the time frame, the maximum relationship is counted.

Number of Participants Reporting Adverse Events of Special Interest (AESIs)Measured through Month 18

There were no adverse events of special interest reported by any participant.

Number of Participants Reporting New Chronic Conditions (Requiring Medical Intervention for >= 30 Days)Measured through Month 18

New chronic conditions are adverse events that require medical intervention for \>= 30 days.

Number of Participants With Early Study Termination Associated With an AE or ReactogenicityMeasured through Month 18

There were no early study terminations associated with an AE or reactogenicity reported by any participant.

Number of Participants With Study Product Discontinuation Associated With an AE or ReactogenicityMeasured through Month 18

From the study product discontinuation form, study product discontinuation reasons are tabulated by treatment arm.

Chemistry and Hematology Laboratory Measures - Platelets, WBCMeasured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455

For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

Numbers of Participants With Grade 1 or Higher Local Laboratory ResultsMeasured during screening, Days 0, 1, 3, 7, 42, 84, 85, 87, 91, 98, 182, 378, and 455

The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the DAIDS AE Grading Table were tabulated by treatment arm for each post-vaccination time point.

Secondary Outcome Measures
NameTimeMethod
Vaccine-induced Occurrence of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the VaccineMeasured at Months 6.5, 12, 12.5, and 18

PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Any Env magnitude is the maximum of 1086 gp120, TV1 gp120, and Env ZM96 magnitudes. Any HIV magnitude is the sum of Any Env and LAI Gag magnitudes. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

Occurrence of Vaccine-induced Serum IgG3 Ab Binding to Env ProteinsMeasured at Months 12.5 and 18.

Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

Level of Vaccine-induced Serum IgG3 Ab Binding to Env ProteinsMeasured at Months 12.5 and 18.

Serum IgG3 responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:40 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).

Level of Vaccine-induced Serum IgA Ab Binding to Env ProteinsMeasured at Months 6.5 and 12.

Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).

Vaccine-induced Percentage of CD4+ T-cells Expressing Markers in Response to HIV Proteins Included in the VaccineMeasured at Months 6.5, 12, 12.5, and 18

PBMC samples are stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing markers (IFNg and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. A contingency table is constructed to assess response: stimulation (peptide/none) vs. marker expression (yes/no). A one-sided Fisher's exact test is applied, testing if the number of cells positive for the marker is equal in the stimulated vs. unstimulated cells. A discrete Bonferroni adjustment is made over the peptide pools. Response is positive if adjusted p-value \<=0.00001. Any Env magnitude is the maximum of 1086 gp120, TV1 gp120, and Env ZM96 magnitudes. Any HIV magnitude is the sum of Any Env and LAI Gag magnitudes. Data are excluded if blood draw date was outside the visit window, participant was HIV-infected, PBMC viability or T-cell count were low, or negative control was high.

Occurrence of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)Measured at Months 12.5 and 18.

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

Occurrence of Vaccine-induced Serum IgG Ab Binding to V2 Env ProteinsMeasured at Months 12.5 and 18.

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

Level of Vaccine-induced Serum IgG Ab Binding to V2 Env ProteinsMeasured at Months 12.5 and 18.

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).

Occurrence of Vaccine-induced Serum IgA Ab Binding to Env ProteinsMeasured at Months 6.5 and 12.

Serum IgA responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:10 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Samples from post-enrollment visits have positive responses if they meet three criteria: (1) net MFI greater than or equal to an antigen-specific response threshold (defined as the maximum of 100 and the 95th percentile of baseline net MFI), (2) net MFI values are greater than 3 times baseline net MFI, and (3) experimental antigen MFI values are greater than 3 times baseline MFI.

HIV-specific CD4+ T Cell Polyfunctionality by ICS - Functionality ScoresMeasured at Months 6.5, 12, 12.5, and 18

COMPASS uses a Bayesian hierarchical framework to model all observed functional cell subsets and select those most likely to exhibit antigen-specific responses. Cell-subset responses are quantified by posterior probabilities. The functionality score (FS) summarizes, as a single number for each participant, the proportion of antigen-specific cell subsets among all measured subsets, irrespective of degree of functionality. FS ranges from zero to one. FS will assign a higher score to participants that exhibit antigen specificity in more cell subsets irrespective of their degree of functionality.

HIV-specific CD4+ T Cell Polyfunctionality by ICS - Polyfunctionality ScoresMeasured at Months 6.5, 12, 12.5, and 18

COMPASS uses a Bayesian hierarchical framework to model all observed functional cell subsets and select those most likely to exhibit antigen-specific responses. Cell-subset responses are quantified by posterior probabilities. The polyfunctionality score (PFS) summarizes, as a single number for each participant, the proportion of antigen-specific cell subsets among all measured subsets, weighted by the degree of functionality of the corresponding subset. PFS ranges from zero to one. PFS will assign a higher score to participants with antigen-specific cell subsets of higher degree.

Level of Vaccine-induced Serum IgG Ab Binding to the 3 gp120 Env Proteins Contained in the Vaccine Regimen (ZM96, TV1.C, and 1086.C)Measured at Months 12.5 and 18.

Serum IgG responses were measured on a Bio-Plex instrument using a standardized custom Luminex assay, run at 1:50 dilution. The readout is background-subtracted mean fluorescent intensity (MFI), with background adjustment for an antigen-specific plate level control. For each sample, response magnitude is net MFI, defined as experimental antigen MFI minus reference antigen MFI. Net MFI \< 1 is set to 1, and net MFI \> 22,000 is set to 22,000. Data are excluded if blood draw date was outside the allowable window, a participant was HIV-infected, reference antigen \> 5,000 MFI, or baseline net MFI \> 6,500. Summary was calculated among positive responders only (positivity criteria are described in Outcome 1).

Trial Locations

Locations (6)

Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS

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Maputo, Mozambique

Seke South CRS

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Chitungwiza, Mashonaland East, Zimbabwe

Emavundleni CRS

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Cape Town, Western Cape, South Africa

Aurum Tembisa CRS

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Johannesburg, Gauteng, South Africa

Soweto HVTN CRS

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Johannesburg, Gauteng, South Africa

eThekwini CRS

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Durban, Kwa Zulu Natal, South Africa

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