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An Oil-in-Water adjuvant significantly increased influenza A/H7N9 split virus Vaccine-Induced circulating follicular helper T (cT) cells and antibody responses.

2022 Nov 22

Journal Article

Lai, L.; Rouphael, N.; Xu, Y.; Kabbani, S.; Beck, A.; Sherman, A.; Anderson, E.J.; Bellamy, A.; Weiss, J.; Cross, K.; Mulligan, M.J.








Adjuvants, Immunologic; Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; Hemagglutination Inhibition Tests; Humans; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Influenza, Human; Polysorbates; Squalene; Water

BACKGROUND: Unadjuvanted A/H7N9 vaccines are poorly immunogenic. The immune response is improved with the addition of MF59, an oil-in-water adjuvant. However, the cellular immunologic responses of MF59-adjuvanted A/H7N9 vaccine are not fully understood.METHODS: 37 participants were vaccinated with 2 doses of 2013 influenza A/H7N9 vaccine (at Days 1 and 21) with or without MF59 and enrolled in an immunology substudy. Responses were assessed at multiple timepoints (Days 0, 8, 21, 29, and 42) for hemagglutination inhibition (HAI) and neutralizing antibody (Neut) assays, memory B cell responses by enzyme-linked ImmunoSpot; circulating follicular helper T cells (cT) and CD4 + T cells by intracellular cytokine staining.RESULTS: MF59-adjuvanted influenza A/H7N9 vaccine induced significantly higher hemagglutination inhibition (HAI) and neutralizing antibody (Neut) responses when compared to unadjuvanted vaccine. The adjuvanted vaccine elicited significantly higher levels of Inducible T-cell Co-Stimulator (ICOS) expression by CXCR3CXCR5CD4 cT cells, compared to unadjuvanted vaccine. The magnitude of increase in cT cells (from baseline to Day 8) and in IL-21 expressing CD154CD4 T cells (from baseline to Days 8 and 21) correlated with HAI (at Day 29) and Neut antibody (at Days 8 and 29) titers. The increase in frequency of IL-21 expressing CD154CD4T cells (from baseline to Day 21) correlated with memory B cell frequency (at Day 42).CONCLUSION: cT activation is associated with HAI and Neut responses in recipients of MF59-adjuvanted influenza A/H7N9 vaccine relative to unadjuvanted vaccine. Future studies should focus on optimizing the cT response and use cT as an early biomarker of serological response to vaccination. This trial was registered at, trial number NCT01938742.

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