Oral Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2026

Historic 1994 Influenza Vaccine Cohorts Defines Breadth of Antibody and B Cell Responses Towards Three Decades of Future Influenza A and B Viruses (#51)

Isabelle JH Foo 1 , Thi HO Nguyen 1 , Ruth A Purcell 1 , Hyon-Xhi Tan 1 , Georgia Deliyannis 1 , Wuji Zhang 1 , Louise Carolan 2 , A. Jessica Hadiprodjo 2 , Howard H Huang 1 , Lilith F Allen 1 , Ruth R Hagen 1 , L. Carissa Aurelia 1 , Hayley A McQuilten 1 , Louise C Rowntree 1 , Lukasz Kedzierski 1 , Samuel H Wilks 3 4 , Matthew R McKay 1 3 4 , Gregory A Tannock 5 , Stephen J Kent 1 6 , Karen Laurie 7 , Annette Fox 2 8 , Steven Rockman 1 7 , Lorena E Brown 1 , Amy W Chung 1 , Adam K Wheatley 1 , Katherine Kedzierska 1
  1. The University of Melbourne, Melbourne, VICTORIA, Australia
  2. WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VICTORIA, Australia
  3. Department of Electrical and Electronic Engineering, University of Melbourne, Melbourne, Victoria, Australia
  4. Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  5. Burnet Institute, Melbourne, Victoria, Australia
  6. Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Monash University, Melborune, Victoria, Australia
  7. Vaccine Product Development, CSL Seqirus Ltd, Melbourne, Victoria, Australia
  8. Department of Infectious Diseases, University of Melbourne, Melbourne, Victoria, Australia

Influenza remains a significant global health problem, causing seasonal annual epidemics and occasional pandemics. Immunization with the inactivated influenza vaccine (IIV) is currently the most effective strategy to combat seasonal influenza infections. IIVs elicit neutralising antibodies directed towards surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), stemming from vaccine-induced strains, activates B-cells and T follicular helper (Tfh) cells and induce antibody-secreting cells (ASCs). The breadth of vaccine-induced humoral immunity towards future differentially-evolving influenza A and B viruses is, however, generally 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. To date, this is the most forward longitudinal study following influenza vaccination that detects antibody and B cell responses towards future influenza viruses across 3 viral subtypes and age groups. 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 younger and older adults. Antibodies towards future H1N1 strains were detected across younger and older adults, which included non-neutralising HA stem antibody responses. Interestingly, older adults 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. Prominent boosting against earlier B/Yamagata/16/1988 and future Yamagata-lineage strains were also observed across younger and older adults, but antibody responses towards future rapidly-evolving H3N2 strains were minimal. Systems serology revealed that, at baseline before 1994 vaccination, older adults comprised divergent antibody signatures against future antigens featuring mature IgA1 responses, while younger adults featured more naive IgM responses. However, post-vaccination responses were of high-quality in both age groups.

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. Group 1 cross-reactive H1/H5 stalk-specific responses also contributed to the overall H1 future response, whereas cross-reactive H3/H7 stalk-specific B cells were not detected.

Overall, using a unique 1994 vaccinated cohort, 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 highlights the unmet need to optimise future vaccine strategies, especially for H3N2.