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Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.

C Buddy Creech·Kristen J Steenbergen·Casey E Gelber·Leigh M Howard·Kevin L Schey·Kristie Lindsey Rose·Sandra M Yoder·Kathryn M Edwards·Johannes B Goll
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Abstract

INTRODUCTION: Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood. METHODS: We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that. RESULTS: AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood. DISCUSSION: Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

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AdultFemaleHumansMaleAdjuvants, Immunologicalpha-TocopherolAntibodies, ViralDrug CombinationsGene Expression ProfilingInfluenza A Virus, H7N9 SubtypeInfluenza VaccinesInfluenza, HumanPolysorbatesProteomeProteomicsSqualeneTranscriptomeAS03H7N9adjuvantsavian influenzainfluenzainfluenza vaccineproteomicssystems biologyClinical Trial, Phase IIJournal ArticleRandomized Controlled Trial

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C Buddy Creech, Kristen J Steenbergen, Casey E Gelber, Leigh M Howard, Kevin L Schey, Kristie Lindsey Rose, Sandra M Yoder, Kathryn M Edwards, Johannes B Goll. 2026-08-07. Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.. https://doi.org/10.3389/fimmu.2026.1786231

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