Immunogenicity of Twice-annual Vaccination against Seasonal Influenza for Two Hemispheres in Elderly in Hong Kong

Abstract

Introduction and Project Objectives In the winter of 2014-15, emergence of a drifted non-matched influenza A(H3N2) strain led the Centre for Health Protection to administer the 2015 southern hemisphere (SH) seasonal influenza vaccine (SIV) for the older adults. An observational study was conducted to assess the immunogenicity of the SH SIV among older adults in Hong Kong and its effect on the immunogenicity of subsequent NH SIV in 2015-16. Methods In the summer of 2015 we enrolled older adults ≥75 years old who were receiving SH SIV, and collected pre- and post-vaccination sera (Group A1). We followed up these older adults through to the winter of 2015-16 when they received NH SIV and again collected pre- and post-vaccination sera (Group A2). For comparison we enrolled a separate group of older adults who received NH SIV in winter 2015-16 without prior receipt of the 2015 SH SIV (Group B2). We tested the sera against vaccine strains by haemagglutination-inhibition (HAI) assays. A subgroup of participants in each group had additional blood specimens collected pre- and post-vaccination for additional tests on cell-mediated immunity. Results We enrolled 978 people involving 470 vaccinations in Group A1, 419 vaccinations in Group A2 and 408 vaccinations in Group B2. In comparison with Group A1, Group A2 had significantly higher geometrical mean titre (GMT) ratios and proportions of seroconversion at Day 30 for A(H1N1) and B/Victoria but lower for A(H3N2) and B/Yamagata, and significantly higher proportions of seroprotection at Day 30 for influenza A (H1 and H3) but similar for both lineages of influenza B. In comparison with Group B2, significantly lower GMT ratios and proportions of seroconversion at Day 30 were observed across all four vaccine strains in Group A2. The proportions of seroprotection at Day 30 were higher in Group B2 than Group A2 for A(H3N2) and B/Yamagata but similar for A(H1N1) and B/Victoria. A significant reduction in responses of A(H3N2)-specific CD4 T cells with effector memory phenotype was seen after twice-annual vaccination but had only a modest association with low HAI GMT rises for the homologous virus. Conclusions There was blunting of immune responses in the twice-annual vaccination group compared to once-annual vaccination group, while protection was likely to have been improved during the summer for the twice-annual vaccination group that did receive SH vaccination. The relationship between twice-annual vaccination and reduced CD4 memory responses for impaired helper functions for antibody generation requires further exploration.