Poster Presentation 16th Lorne Infection and Immunity 2026

Historic 1994 influenza vaccine cohorts defines breadth of antibody and B cell responses towards three decades of future influenza A and B viruses (131662)

Oanh Nguyen 1 , Isabelle Foo 1 , Ruth Purcell 1 , Hyon-Xhi Tan 1 , Georgia Deliyannis 1 , Wuji Zhang 1 , Louise Carolan 2 , Jessica Hadiprodjo 2 , Howard Wong 1 , Lily Allen 1 , Ruth Hagen 1 , Carissa Aurelia 1 , Hayley McQuilten 1 , Louise Rowntree 1 , Lukasz Kedzierski 1 , Sam Wilks 3 , Matthew McKay 1 , Greg Tannock 4 , Stephen Kent 1 , Karen Laurie 5 , Annette Fox 2 , Steven Rockman 5 , Lorena Brown 1 , Amy Chung 1 , Adam Wheatley 1 , Katherine Kedzierska 1
  1. Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne
  2. World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza, at The Peter Doherty Institute for Infection and Immunity , Melbourne
  3. Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne
  4. Burnet Institute, Melbourne, VIC, Australia
  5. Vaccine Product Development, CSL Seqirus Ltd, Parkville, VIC, Australia

Influenza vaccination is the best way to combat annual influenza epidemics, yet the breadth of vaccine-induced humoral immunity towards decades of future differentially-evolving influenza A and B viruses is unclear. Using historic 1994 influenza vaccination cohorts of young and older adults, we defined antibody responses elicited by 1994 vaccination against future influenza strains spanning three decades of differentially-evolving influenza A (FLUAV) and B (FLUBV) viruses. Quality of antibody responses together with vaccine-induced and cross-reactive B-cell memory responses were investigated. Vaccination increased antibody titers against all 1994 vaccine components (H1N1 A/Texas/36/1991, H3N2 A/Beijing/32/1992, Yamagata B/Panama/45/1990) in young adults, but not B/Panama/45/90 in older adults. Antibodies towards future H1N1 strains were detected across younger and older adults. Older adults, additionally displayed boosted responses towards A/Michigan/45/2015, related to the 2009 pandemic strain known to induce cross-reactive antibodies with 1918-like H1N1 viruses. Antibody responses towards future rapidly-evolving H3N2 strains were minimal. Prominent boosting against earlier B/Yamagata/16/1988 and future Yamagata-lineage strains were found across younger and older adults. Individuals who responded strongly to B/Panama/45/1990 also responded to future FLUBV strains from Yamagata and Victorian lineages. Systems serology revealed qualitative differences in antigen-antibody signatures between younger and older adults at baseline before 1994 vaccination, with serological features towards vaccine antigens overlapping post-vaccination. Older adults, however, comprised divergent antibody signatures against future antigens featuring mature-IgA1 responses, while younger adults featured more naive-IgM responses. To define cross-reactive B-cell responses, fluorescently-labelled recombinant HA-probes were generated for vaccine and future influenza strains. 1994 vaccination induced cross-reactive memory B-cells towards vaccine and future H1 and FLUBV strains, but minimal responses for H3. Our study provides key insights into the breadth of vaccine-induced humoral immunity towards future influenza viruses over 30-years of FLUAV and FLUBV evolution, including newly-emerging pandemic strains, and the need to optimize future vaccine strategies, especially for rapidly-evolving H3N2s.