Hinojosa 2021 evaluated effects of Ab landscapes on vaccine responses using sera collected from children over two influenza seasons and found that A(H3N2) Ab landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.
Milestone
2.4.b
Repeat vaccination
In progress
High priority
Determine through birth-year cohort or clinical studies how repeated influenza vaccinations affect immune responses to subsequent influenza vaccinations, including immune responses to HA, NA, and other antigens.
Progress Highlights
Fox 2025 conducted a retrospective serologic analysis of clinical samples collected during the PIVOT (Potent Influenza Vaccination strategies in Older adults—randomized immunogenicity) Trial in Hong Kong comparing Ab responses following adjuvanted, high-dose, recombinant HA, or standard dose seasonal influenza vaccine administration annually, or not at all, for 5 years. Results suggested that adjuvanted and recombinant HA vaccines may improve breadth of protection against H3N2 influenza viruses but may not overcome attenuating effects of repeated vaccination.
Cowling 2024 conducted a randomized clinical trial of repeat influenza vaccination with Flublok (Sanofi) in Hong Kong as part of the DRIVE study; preliminary results from the first 2 years of the study found that repeat and first-time vaccinees had similar postvaccination geometric mean titers to all four seasonal influenza vaccine strains, indicative of similar levels of clinical protection.
Shannon 2024 examined how the CD4 T-cell response to IIV is established and develops throughout early childhood by quantifying influenza-specific CD4 T-cell responses following IIV over two influenza seasons in 47 vaccinated children who had no documented history of natural influenza infection during the study. Results showed that IIV elicits a CD4 T-cell response to H3 and HAB, with increases in the magnitude of the CD4 T-cell response and changes in cellular functionality throughout childhood.
Zhang 2024, in a prospective observational cohort study in China, examined Ab changes and B-cell receptor repertoire characteristics among 100 subjects singly or repeatedly immunized with influenza vaccines including 3C.2a1 or 3C.3a1 A(H3N2) during the 2018–2019 and 2019–2020 influenza seasons. They found that vaccination elicited cross‐reactive Ab responses against future emerging strains and observed broader nAbs to A(H3N2) viruses and more diverse B-cell repertoires in the repeated vaccination group.
Sung 2023 analyzed associations between host factors and antibody responses in a repeated vaccination setting, finding disparate vaccine-elicited immune responses in adults when they were repeatedly vaccinated for at least two seasons, such as interactive effects between age and BMI on overall immune responses and between sex at birth and BMI in the adult age group.
Jones-Gray 2022 found through a meta-analysis of 41 published studies that vaccination in two consecutive years provides better protection than no vaccination, even though vaccination in the previous year attenuates vaccine effectiveness.
NCT05110911: NIAID award R01AI141534 to the University of Melbourne to investigate the long-term consequences of repeated annual influenza vaccination among healthcare workers (not a birth-year cohort study).