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Influenza vaccine responses differ between young children previously exposed to influenza antigens via infection versus vaccination

Year: 2026

Type: article

Abstract: Annual influenza vaccination is recommended for young children with limited understanding of how this may imprint influenza immunity. We conducted a pilot study to examine whether early life exposure to influenza through vaccination versus infection affects subsequent vaccination responses. Nineteen children aged 6–60 months were enrolled at two Australian hospitals during 2019–2021. Plasma was collected before and after vaccination for up to three successive years to measure antibody titres by hemagglutinination (HA) and neuraminidase (NA) inhibiting (HI, NI) assays and ELISA. Medical records and seropositivity (HI titre ≥40) at enrolment were used to classify seven children as having prior vaccination(s) and eight as having prior influenza A(H3N2) infection. Others had mixed, no, or unclear prior exposures. Post-vaccination antibody titres and seroconversion (HI fold-rise ≥4) were compared across the two main prior exposure groups. Here we show that post-vaccination HI and NI antibody titres and titre-rises against A(H3N2) are far higher among children classified as having had prior A(H3N2) infection compared to prior vaccination; 8/8 versus 3/7 seroconverted, respectively. A(H3N2) HA-stem binding antibody titres are modest but rise more after vaccination among children classified as having had prior A(H3N2) infection. A(H1N1)-reactive antibody responses are not significantly different between groups. These results suggest that for priming subsequent vaccine antibody responses against A(H3N2), infection may be superior to vaccination. Our first exposures to viruses that constantly evolve and re-infect us throughout life may direct our subsequent immune responses to that virus. Influenza vaccination could imprint immunity differently from natural infection depending on the vaccine formulation, which is commonly a mix of detergent-treated, inactivated egg-grown viruses. Our pilot study examined whether children who had evidence of early life exposure to influenza through infection versus vaccination respond differently to influenza vaccination. We found that children with evidence of prior influenza A(H3N2) virus infection had substantially greater antibody responses against A(H3N2) viruses than children with prior vaccination whereas antibody responses against other vaccine components were similar. These pilot study results suggest that influenza infection in early life enhances subsequent influenza vaccine responses. Fox et al. investigate how early life exposures to influenza shape antibody responses. They show that antibody responses to vaccination are better among children who had previously been infected.

Source: Communications Medicine