A key goal of our work is to identify factors that contribute to the variable and sometimes poor immunogenicity of seasonal influenza vaccines. Influenza viruses are constantly evolving, and therefore, influenza vaccine strains are frequently updated and re-administered. The immunogenicity and effectiveness of seasonal influenza vaccines can vary substantially between seasons, and can be particularly poor against A(H3N2) viruses, and among people who have been vaccinated in multiple successive years. Our studies aim to understand how prior influenza virus infections and vaccinations impact upon responses to new vaccine strains. In particular, we are investigating if, and how, existing immunity alters the capacity of vaccines to induce B cells/antibodies against new vaccine strain epitopes, and hence update immunity.
Our research platform is built on a series of influenza vaccination studies among populations who have variable and well-characterised infection or vaccination histories. Internationally collaborative studies have been conducted across a range of geographic locations and over multiple years, to provide a comprehensive analysis of vaccine immunogenicity.
A series of experimental tools has been established in our lab to characterise B cell and antibody responses to influenza virus infection. Analyses are specifically designed to determine the strain coverage of antibodies induced by vaccination, and the extent to which recalled memory B cells against epitopes shared with past strains dominate responses. Recombinant heamgglutinin probes are use to detect and characterise B cells that are specific for the vaccine strain or that are cross-reactive with past strains. B cell receptor sequencing and expression are used to determine whether B cells are naïve or memory derived. Reverse engineered viruses are used to determine the epitopes recognized by polyclonal sera or by antibodies derived from individual recalled memory B cells. Extensive data generated by these projects is being used to develop models to better quantify how exposure history and memory recall may shape or limit influenza vaccine immuongenicity and effectiveness.
- Louise Carolan, Research Assistant
- Yue-Yang (Ryan) Tseng, Post-Doctoral Research Fellow
- Maria Auladell, PhD Student
- NHMRC Project Grant APP1103367, 2015-2020, CIA
- NIH Research Project Grant R01AI141534, 2019-2024, Co-PI
- US CDC Contract BAA 75D301-19-R-67835, Co-PI 2019-2021
- Hong Kong University Contract, Co-PI 2020-2021
- NIH CEIRS NYICE subcontract, CEIRS-Option 12B Rochester 2019
- Hoa LNM, Sullivan S, Mai LQ, Khvorov A, Phuong HVM, Hang NLK,Thai PQ, Thanh LT, Carolan L, Anh DD, Duong TN, Bryant JE, van Doorn HR, Wertheim H, Horby P, Fox A. Influenza A(H1N1)pdm09 But Not A(H3N2) Virus Infection Induces Durable Seroprotection: Results From the Ha Nam Cohort, J Infect Dis. 2020 , https://doi.org/10.1093/infdis/jiaa293
- Auladell M, Nguyen TH, Garcillán B, Mackay F, Kedzierska K, Fox A. Distinguishing naive- from memory-derived human B cells during acute responses. Clin Transl Immunology. 2019; 8(11):e01090. PMID: 31844520.
- Fox A, Mai LQ, Thanh LT, Wolbers M, Hang NLK, Thai PQ, Horby P. Hemagglutination inhibiting antibodies and protection against seasonal and pandemic influenza infection J Infect. 2015. 70(2) 187-196.
- Fonville JM, Wilks SH, James SL, Fox A, Ventresca M, Aban M,…, Smith DJ. Antibody landscapes after influenza virus infection or vaccination Science. 2014; 346(6212) 996-1000. PMID: 25414313
- Thai PQ, Mai LQ, Welkers MR, Hang NLK, Thanh LT, Dung VT,.., Fox A. Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort J Infect. 2014; 68(6) 581-590. PMID: 24491598
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