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

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 (cTFH) and CD4 + T cells by intracellular cytokine staining.Results: MF59-adjuvanted influenza A/H7N9 vaccine induced significantly higher hemagglutination inhi-bition (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 CXCR3+CXCR5+CD4+ cTFH cells, compared to unadjuvanted vaccine. The magnitude of increase in cTFH cells (from baseline to Day 8) and in IL-21 expressing CD154+CD4+ 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 CD154+CD4+T cells (from baseline to Day 21) correlated with memory B cell frequency (at Day 42).Conclusion: cTFH 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 cTFH response and use cTFH as an early biomarker of serological response to vaccination. This trial was registered at clinicaltrials.gov, trial number NCT01938742.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

This study found that the use of MF59 adjuvant in A/H7N9 influenza vaccine enhances the immune response compared to the unadjuvanted vaccine. The activation of cTFH cells is associated with hemagglutination inhibition and neutralizing antibody responses, suggesting that cTFH can be used as an early biomarker for the serological response to vaccination.