Journal Article

The role of influenza Hemagglutination-Inhibition antibody as a vaccine mediator in children

Morgan, Rebecca L., Pullenayegum, Eleanor, Motaghi, Shahrzad, Loeb, Mark

2024

Overview

•Understanding the mechanism of influenza vaccine protection in children can inform future vaccine development.•Most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI.•For influenza B, HAI appeared to mediate most of the vaccine effectiveness, but this was not confirmed by microneutralization. Influenza vaccination may protect through the humoral immune response, cellular immune response, or possibly both. Immunity after vaccination can be mediated through antibodies that may be detected by the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through antibodies by measuring the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (direct effect) for influenza A and B. We analysed data from a cluster randomized trial conducted during the 2008–2009 season in which Canadian Hutterite children were vaccinated against influenza. We used inverse probability weighting to calculate the indirect and direct effect of vaccination against influenza A/H3N2 and influenza B/Brisbane using HAI titres and overall vaccine efficacy. We included data on 617 children from 46 Hutterite colonies, aged between 3 and 15 years who were vaccinated with either inactivated trivalent influenza vaccine or hepatitis A vaccine. Vaccine efficacy was 63 % for influenza A (H3N2) and 28 % for influenza B. The hazard ratio for protection against influenza A/H3N2 due to an indirect effect of vaccination was 0.96 (95 % confidence interval (CI) of 0.00 to 2.89) while for the direct effect it was 0.38 (95 % CI of 0.00 to 5.47). The hazard ratio for influenza B indirect effect was 0.75 (95 % CI of 0.07 to 1) and for the direct effect 0.96 (95 % CI of 0.00 to 12.02). In contrast, repeating the analysis using microneutralization in a subgroup of 488 children revealed that the protective effect for vaccination for A/H3N2 was entirely mediated by antibodies but only for 13 % for influenza B. Although vaccination provided higher protective effectiveness against influenza A than B, most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI titres. In contrast, for influenza B, while the HAI titres appeared to mediate most of the vaccine effectiveness, this was not confirmed by microneutralization analysis.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adolescent / Age / Allergy and Immunology / Antibodies / Antibodies, Viral - blood / Antibodies, Viral - immunology / blood serum / Canada / cell-mediated immunity / Child / Child, Preschool / Children / confidence interval / Effectiveness / Female / hazard ratio / hemagglutination / Hemagglutination inhibition / Hemagglutination Inhibition Tests / Hemagglutination inhibition titer / Hepatitis A / Humans / Humoral immunity / Immune response / Immune response (cell-mediated) / Immune response (humoral) / Immune system / Immunization / Immunology / Infections / Influenza / Influenza A / Influenza A Virus, H3N2 Subtype - immunology / Influenza B / Influenza B virus - immunology / influenza vaccination / Influenza vaccine / influenza vaccines / Influenza Vaccines - administration & dosage / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - prevention & control / Male / Mediation analysis / Older people / protective effect / Public health / Randomized controlled trial / Statistical analysis / Subgroups / Vaccination / Vaccine Efficacy / Vaccines / Vaccines, Inactivated - administration & dosage / Vaccines, Inactivated - immunology