A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Study Overview
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Brief Summary
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A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. Eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019, 2019-2020, 2020-2021, and 2021-2022).

Detailed Description
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This four-year, pragmatic, prospective study will compare the effectiveness of licensed egg-based inactivated influenza vaccines to the effectiveness of two other types of licensed vaccines, the cell-culture based inactivated influenza vaccine and the recombinant influenza vaccine, in the prevention of laboratory-confirmed influenza infection in active duty members, military retirees, and other DoD beneficiaries. Military treatment facilities (MTFs) in the United States will participate in this protocol. Enrollment will be restricted to adults (≥18 years and older) who are preparing to receive seasonal influenza vaccination at participating DoD sites. Subjects will be randomized to receive one of the three licensed influenza vaccines types for evaluation of effectiveness. There is no exclusion for pregnancy, as none of these licensed products are contraindicated in pregnant women.

Official Title
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A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

Conditions
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Influenza, Influenza-like Illness, Influenza Vaccines

Intervention / Treatment
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* Biological: Egg based influenza vaccines
* Biological: Recombinant influenza vaccines
* Biological: Cell-culture based influenza vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for care in Department of Defense medical facilities (Defense Enrollment Eligibility Reporting System eligible) ≥18 years of age. At a participating Military Treatment Facility site for the purpose of receiving a seasonal (2018-2019, 2019-2020,2020-2021, 2021-2022) influenza vaccination. Able to speak English and able to provide informed consent Able to receive and respond to texts and/or emails, or a military recruit Exclusion Criteria: Adults intending to receive or who have received the current seasons FluMist Vaccine (LAIV) Adults who have already received a flu vaccine within the current season Individual who cannot receive a flu vaccine or standard dosing due to another medical condition Allergic to gentamicin, polymyxin and/or neomycin Individuals who fail to meet the inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 18,000 eligible subjects (or 6,000 subject distributed evenly between the 3 study arms) will be enrolled. eligible subjects will be randomized in 1:1:1 (cell-culture-based vaccine, the recombinant vaccine, or the egg-based vaccine) over four influenza seasons (2018-2019,2019-2020, 2020-2021, and 2021-2022).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Egg based influenza vaccines<br>Quadrivalent egg-based vaccines, which contain an inactivated form of the virus. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. All egg-based vaccines are FDA licensed for use in the United States. | Biological: Egg based influenza vaccines<br>* Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.<br>|
| Active Comparator: Recombinant influenza vaccines<br>FluBlok, recombinant HA influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flublok Quadrivalent is a quadrivalent recombinant influenza vaccine that has been licensed by the FDA for use in the United States. | Biological: Recombinant influenza vaccines<br>* Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.<br>|
| Active Comparator: Cell-culture based influenza vaccines<br>Flucelvax, Madin-Darby canine kidney (MDCK)-cell-culture based inactivated influenza vaccine. Vaccines will be given to the participant in accordance with standard clinical practices for those in the US military. Flucelvax quadrivalent, the only cell-based flu vaccine FDA licensed for use in the United States. | Biological: Cell-culture based influenza vaccines<br>* Participants will be randomly allocated to one of three vaccine types in accordance with standard clinical practices for those in the US military. All vaccines are FDA licensed for use in the United States.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Laboratory Confirmed Influenza | Laboratory-confirmed influenza as ascertained by a sensitive and specific assay. | Onset > 13 days after vaccination up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemagglutination Inhibition (HI) Titer Responses to Influenza Vaccine Strains. | Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay. | Baseline to 21-35 days post vaccine | 
| Pseudovirion Neutralization (PVN) Responses to Influenza Vaccine. | Neutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain. | Baseline to 21-35 days post vaccine | 
| Anti-Neuraminidase (Anti-NA) Titer Responses to Influenza Vaccine. | Anti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay. | Baseline to 21-35 days post vaccine | 
| Number of Participants With Influenza-Like Illness | Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance. | Onset > 13 days after vaccination up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine