Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations

Phase 4

Completed

Conditions: Influenza
COVID-19

Interventions: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster)
Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster)
Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)

Registration Number: NCT06020118

Lead Sponsor: Duke University

Brief Summary: This is a prospective, randomized randomized immunologic study of response to influenza and SARS-CoV-2 vaccination across four of the US Influenza Vaccine Effectiveness (Flu VE) Network study sites.

Detailed Description: This study is a prospective, randomized comparative immunogenicity study in an enrolled cohort. During this study, eligible participants will be randomly assigned to receive an approved quadrivalent cell culture-based influenza vaccine (ccIIV4, Seqirus) and an approved mRNA COVID-19 vaccine (Moderna) either concomitantly or sequentially, 28 days apart. Participants (aged 6-11 years and 18-64 years) will be enrolled in the 2023-2024 influenza season.

Demographic and health data (including influenza and COVID-19 vaccination and infection history) will be collected upon enrollment. Enrolled participants will be randomized to one of the following interventions (2:1:1) (i) concomitant administration of the mRNA COVID-19 vaccine (Moderna) and quadrivalent influenza vaccine (ccIIV4, Seqirus); (ii)sequential administration of the quadrivalent influenza vaccine (ccIIV4, Seqirus) at Visit 1 (day 0) and the mRNA COVID-19 vaccine(Moderna) at Visit 2 (day 28); (iii) sequential administration of the mRNA COVID-19 vaccine (Moderna) at Visit 1 (day 0) followed by the quadrivalent influenza vaccine (ccIIV4, Seqirus) at Visit 2 (day 28). Participants will not be blinded to vaccine group.

Whole blood samples to isolate sera for immune assays will be collected prior to vaccination administration at Visit 1 (day 0), Visit 2 (day 28) Visit 3 (day 56; post-vaccination 2) and Visit 4 (day180; end of local flu circulation). Blood samples to isolate PBMC and plasma will be collected from a subset of 250 participants (200 adults and 50 children). If participants exhibit ARI during the study period, the participants may be asked to present for collection of a nasal swab for viral testing for acute influenza or SARS-CoV-2 infection (within 10 days after symptom onset), and blood specimen to isolate sera for immune assays. For participants with confirmed acute infection, the participants may be asked to present for collection of a convalescent-phase blood specimen approximately 28 days after acute visit for isolation of sera, PBMC and plasma.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 455

Inclusion Criteria

Healthy children aged 6-11 years and healthy adults aged 18-64 years that have not received the current season's influenza vaccination or a mRNA COVID-19 vaccination in the past 6 months and have already completed at least a two-dose primary series of an mRNA COVID-19 vaccination
English or Spanish literate
Email or text message capability for weekly follow-up
Intention of receiving influenza vaccine and mRNA COVID-19 vaccine based on ACIP-CDC guidelines
Willing to provide written/electronic informed consent
Intention of being available for entire study period and able to complete all relevant study procedures, including follow-up phone calls and clinic visits

Exclusion Criteria

Self-reported COVID-19 infection within 3 months prior to enrollment
Received COVID-19 vaccine within 6 months prior to enrollment
Received influenza vaccine during the respective influenza season in which the participants are being enrolled
< 9 years of age and recommended to receive two doses of IIV4 during the respective influenza season in which they are being enrolled
History of severe allergic reaction after a previous dose of any influenza or COVID-19 mRNA vaccine; or to an influenza or COVID-19 mRNA vaccine component
Receipt of any licensed vaccine within 6 weeks prior to enrollment in this study or planning receipt of any vaccines within 4 weeks after the receipt of the second vaccine dose administered during study procedures
Has an immunocompromising condition or taking immunosuppressive medication*

* Received oral, intramuscular or intravenous systemic immunosuppressants, or immune modifying drugs for >14 days in total within 6 months prior to any study vaccine dose (for corticosteroids ≥ 20 mg/day of prednisone equivalent).

** Note: Topical medications are allowed
Received immunoglobulin, SARS-CoV-2 immunoglobulin, SARS-CoV-2 monoclonal antibody, or blood-derived products, within 3 months prior any study vaccine dose.
History of Guillain-Barré syndrome
History of myocarditis or pericarditis
History of multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A)
Currently pregnant, planning to become pregnant within the first three months of the study per participant self-report or likely to be pregnant per screening criteria
Bleeding disorder diagnosed by a healthcare provider or bleeding difficulties with intramuscular injections or blood draws.
Has injury or other reason why deltoid site on both arms cannot be used for vaccinations
Any condition which, in the opinion of the investigators, may pose a health risk to the participant or interfere with the evaluation of the study objectives
Temporary Delay Criteria: History of febrile illness (> 100.0°F or 37.8°C) within the past 72 hours prior to vaccine administration

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group i: Concomitant Vaccination	Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster)	Concomitant Vaccination (Influenza vaccine and mRNA COVID booster) at Visit 1
Group ii: Influenza Vaccination at Visit 1	Sequential Vaccination (Influenza vaccine then mRNA COVID booster)	Sequential vaccination with Influenza vaccination at Visit 1 and mRNA COVID booster at Visit 2
Group iii: mRNA COVID-19 Vaccination at Visit 1	Sequential Vaccination (mRNA COVID booster then Influenza vaccine)	Sequential vaccination with mRNA COVID booster at Visit 1 and Influenza vaccination at Visit 2

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With HAI Seroconversion	Visit 1 (day 1; baseline) to Visit 2 (days 28-42; post-vaccination) for all arms/groups	Number of participants with a seroconversion HAI Titer ≥1:40 at Day 29 if Day 1 titer is \<1:10 or a four-fold rise at Day 29 if Day 1 titer is ≥1:10 for each ccIIV4 antigen in the 2023-2024 influenza season.
Percentage of Participants With HAI Seroprotection	Visit 1 (day 1; baseline; pre-immunization) and Visit 2 (days 28-42; post-immunization) for all arms/groups	Number of participants with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each ccIIV4 antigen in the 2023-2024 influenza season.
HAI Geometric Mean Titer	Visit 1 (day 1; baseline; pre-immunization) and Visit 2 (days 28-42; post-immunization) for all arms/groups	The geometric mean HAI titer (GMT) for each ccIIV4 antigen in the 2023-2024 influenza season. GMTs were derived by using the anti-log of the mean of the log transformed titers.
HAI Geometric Mean Fold Rise (GMFR)	Visit 1 (day 1; baseline) to Visit 2 (days 28-42; post-vaccination) for all arms/groups	GMFRs and 95% confidence intervals were calculated using a t-distribution on log 2-transformed titers.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (8): Valleywise Health Comprehensive Health Center
🇺🇸
Phoenix, Arizona, United States
ASU Biodesign Institute
🇺🇸
Tempe, Arizona, United States
Centers for Disease Control and Prevention
🇺🇸
Atlanta, Georgia, United States
Washington University IDCRU
🇺🇸
Saint Louis, Missouri, United States
University Hospitals Cleveland Medical Center
🇺🇸
Cleveland, Ohio, United States
VA Northeast Ohio Healthcare System (VANEOHS)
🇺🇸
Cleveland, Ohio, United States
Senders Pediatrics
🇺🇸
South Euclid, Ohio, United States
Department of Family Medicine, University of Pittsburgh School of Medicine
🇺🇸
Pittsburgh, Pennsylvania, United States
Valleywise Health Comprehensive Health Center
🇺🇸Phoenix, Arizona, United States