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Dryad

Effect of T cell vaccine in an influenza human challenge model

Evans, Thomas1

Published Dec 11, 2024 on Dryad. https://doi.org/10.5061/dryad.rr4xgxdgt

Data files

Dec 11, 2024 version files 27.07 MB

Abstract

The protection afforded by inactivated influenza vaccines can theoretically be improved by inducing T-cell responses to conserved internal influenza A antigens. We hypothesized that in an influenza-controlled human infection challenge, susceptible individuals receiving a vaccine boosting T cell responses would exhibit lower viral load and decreased symptoms compared to placebo recipients. Healthy European volunteers with microneutralization titers < 20 to the H3N2 challenge strain were randomized double-blind using a permuted-block list with a 3:2 allocation ratio to receive IM MVA expressing H3N2 NP and M1 or placebo. Over six weeks later, participants were challenged intranasally. Nasal swabs were collected twice daily for viral PCR, and symptoms of influenza were recorded through day 11. T-cell responses were monitored both pre- and post-vaccination (0,8, and 28 days) and challenge (0 and 28 days) by ELISpot and multiparameter flow cytometry. There was no significant effect of NVANP+M1 versus placebo on the viral area under the curve (vAUC), symptom scores, individual symptoms, or influenza-like illness in Intent to treat or Protocol Analysis. The MVA-NP+M1 vaccine was well-tolerated and induced three-fold increases in CD4+ and CD8+ T cell responses, with no change in the placebo group (p = <0.001). There was also no correlation between vAUC or symptoms with any of the pre-challenge CD4+ or CD8+ T-cell phenotypes in either vaccinated or placebo participants. The use of an MVA vaccine to expand CD4+ and CD8+ T cells to conserved influenza A antigens in peripheral blood did not impact outcomes in an influenza H3N2 challenge model in seronegative, healthy adults.