In a recent study published in the Journal of Infection, researchers evaluated the impact of the timing of influenza (flu) vaccine administration on vaccine-induced immunity against infection.
Studies have reported that inactivated influenza vaccines confer temporary immune protection against influenza infection among HCWs (healthcare workers) with an elevated risk of influenza virus exposure. Immune responses post-influenza vaccinations have been found to reduce intra-seasonally. However, the significance of antibody waning during the season of influenza is not clear.
About the study
In the present observational prospective cohort study, researchers investigated whether vaccination timing influenced immune protection conferred by influenza vaccinations against infection.
The single-center study was conducted between September and November 2021 and comprised 400 HCWs of the University Hospitals of Leicester NHS (national health service) trust, UK (United Kingdom). The participants were vaccinated with QIV (quadrivalent inactivated influenza vaccine) at two time points before the beginning of the influenza season (between December 2020 and April 2021), i.e., three months prior (early group, n=200) and one month prior (late group, n=200).
The vaccines comprised four antigens of the influenza virus, which were: A/Hong Kong/2671/2019 A/H3N2-like, A/Guangdong-Maonan/SWL1536/2019 A/H1N1pdm-like, B/Phuket/3073/2013-like, and B/Washington/02/2019-like.
For follow-up assessments, monitoring for ILI (influenza-like illness, elevated body temperature >38°C, and cough) and blood samples were required by the participants. Blood samples obtained were analyzed by HAI (haemagglutinin inhibition assays) performed at four different time points, which were: pre-vaccination, three weeks-post vaccination, February 2021 (influenza season peak), and May 2021 (influenza season end).
The seroprotection rates were defined based on the EMEA (European agency for the evaluation of medicinal products) criteria as the proportion of individuals with titers exceeding or equal to 1:40, and those obtained were compared among the two groups at every follow-up visit. Multinomial linear regression modeling was used to evaluate the effects of influenza vaccination timing, sex, age, and previous influenza vaccinations on HAI geometric mean titers (GMTs) at the influenza season peak and season end.
HAI titers were comparable between the two groups of vaccinees across follow-up time points across all influenza virus strains, except for the influenza A/H1N1pdm strain, for which the titers for the early group of vaccines and the late group of vaccinees at influenza season peak were 76 and 99, respectively. The corresponding season-end titers were 54 and 67, respectively.
For influenza A virus (IAV) strains, seroprotection rates did not significantly differ between the two groups of vaccinees at the season peak and end. The influenza B viral strains rates were >98% across follow-up time points. The multinomial analysis showed that the season-peak and season-end HAI assay titers did not significantly differ among the two groups of vaccinees for IAV strains considering sex, age, and previous influenza vaccinations.
In contrast, individuals who were not administered ≥2 influenza vaccinations in the previous four years were associated with lesser HAI GMTs at season-end for the A/H1N1pdm strain (season-peak and season-end adjusted coefficients were -0.7 and -0.8, respectively).
Similar findings were noted for individuals who received multiple influenza vaccinations for Victoria/influenza B virus at season peak (adjusted coefficient -0.4). ILI was reported by sixteen individuals during the follow-up period, none of whom were influenza virus-positive by polymerase chain reaction (PCR)-positive, ten individuals were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, one individual was Rhinovirus-positive, and five individuals were not positive for any of the respiratory viruses tested.
Irrespective of the timing of influenza vaccinations, HAI GMTs following yearly influenza vaccinations were not likely to differ significantly over the forthcoming flu season. Participants vaccinated immediately before the flu season could swiftly generate antibody responses given that GMTs at the season peak showed no differences compared to the early group vaccinees.
Thus, programs of influenza vaccinations must not be halted too early before the flu season commencement to ensure maximal influenza vaccination access for the HCWs. Late vaccine group HCWs showed a greater likelihood toward vaccination reluctance factors, including minor ethnicity and lower age. Thus, early termination of seasonal vaccination programs may reduce the uptake of influenza vaccines for such individuals.
Overall, the study finding showed that among healthy adult individuals, flu vaccine-conferred immune protection did not significantly differ by vaccination timing, underpinning influenza vaccine administration over extended periods for maximizing the uptake of influenza vaccines.