Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

Abstract

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.

Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis

“…96 For influenza B, however, estimates were comparable with their main findings when the analysis was restricted to those patients with no documented influenza B infection in the previous season. 96 41 (49%) of 83 studies were eligible for inclusion in the meta-analysis (appendix pp [10][11][12]. These studies reported a total of 85 type-specific or subtype-specific allage estimates: 19 (23%) for influenza A(H1N1)pdm09, 30 (36%) for influenza A(H3N2), 22 (26%) for influenza B (lineage not specified), five (4%) for influenza B/ Victoria, and nine (11%) for influenza B/Yamagata (figures 2-4 and table 2).…”

“… 5 A 1999 review of ensuing immunological studies identified that roughly half of published serological studies reported reduced post-vaccination antibody titres against A(H3N2) in people who had received multiple influenza vaccinations compared with those who had received a single influenza vaccination. 6 Several subsequent studies have shown diminishing post-vaccination antibody responses 7 , 8 , 9 , 10 , 11 and diminishing vaccine effectiveness 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 as the number of previous vaccines an individual has been given increases.…”

Using Interpretable Machine Learning to Massively Increase the Number of Antibody-Virus Interactions Across Studies

“…The Low Dimensionality of Antibody-Virus Interactions Empowers Matrix Completion Given the vast diversity of antibodies, it is easy to imagine that serum responses cannot inform one another. Indeed, many factors including age, geographic location, frequency/type of vaccinations, and infection history shape the antibody response and influence how it responds to a vaccine or a new viral threat (Kim et al, 2012;Fonville et al, 2014;Thompson et al, 2016;Gouma et al, 2020;Fox et al, 2022).…”

“…Using the age of each subject, these landscapes can quantify how immune imprinting throughout childhood shapes the subsequent antibody response (vinh et al, 2021). In addition, given the growing interest in universal influenza Vaccines capable of inhibiting diverse variants, these high-resolution responses will power studies examining the breadth of the antibody response not just forward in time against newly emerging variants, but also backwards in time to assess how rapidly immunity decays (Carter et al, 2016; Boyoglu-Barnum et al, 2021; Fox et al, 2022). We found that serum potency (the minimum HAI titer against a set of viruses) decreases for more distinct viruses [Figure 7B], as was shown for monoclonal antibodies (Creanga et al, 2021; Einav and Cleary, 2022).…”

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents

“…Whilst results may differ for a highly seronegative population, in our study, restricting analyses to those participants who had HI titres < 40 at baseline did not alter findings with similar results for children and adolescents with and without obesity. Prior vaccination or infection may potentially influence subsequent vaccine responses [ 31 ] and may provide cross-protective immunity against future novel influenza virus exposure [ 32 ]. Our study did not examine cross-protection against non-vaccine strains, however, we did compare seroprotection between participants who had ( n = 20) and had not ( n = 24) received a prior recent influenza vaccine and found similarly high levels of seroprotection.…”