A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD

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.

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

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

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

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.

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.

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.

Plazo: Onset > 13 days after vaccination up to 1 year

Laboratory-confirmed influenza as ascertained by a sensitive and specific assay.

Plazo: Baseline to 21-35 days post vaccine

Strain-specific seroconversion rate determined by reference hemagglutination inhibition assay.

Plazo: Baseline to 21-35 days post vaccine

Neutralizing antibody responses (4-fold rise) to HA-psuedoviruses corresponding to vaccine-matched viruses, recently circulating influenza virus, and emerging influenza strain.

Plazo: Baseline to 21-35 days post vaccine

Anti-Neuraminidase (Anti-NA) titer responses determined by enzyme linked immuno-assay.

Plazo: Onset > 13 days after vaccination up to 1 year

Rate of protocol defined influenza-like illness ascertained by participant response to active surveillance.

Plazo: Onset > 13 days after influenza vaccination up until one year

Laboratory-confirmed SARS CoV2, and SARS CoV2 plus influenza co-infection, as ascertained by nasal swab PCR.

Plazo: onset >13 days after Influenza vaccination up to 1 year

Symptom severity scores were reported by participants using FLU-PRO Plus (Influenza Patient Reported Outcomes), a standardized instrument developed to measure the intensity and frequency of viral respiratory tract symptoms. FluPRO Plus symptom scores range from 0 ("not at all") to 4 ("very much"), with higher scores indicating greater severity.

A Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD