Transcriptomic and Proteomic Signatures Following AS03-adjuvanted Influenza A/H7N9 Vaccine

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. In this study, we used RNA-sequencing and quantitative proteomics to elucidate the response to two doses of influenza A/H7N9 vaccine, with and without AS03 in six immune cell types. These responses were also compared to those seen after administration of an unadjuvanted seasonal influenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccine and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that AS03-adjuvanted vaccine uniquely led to upregulation of immune pathways in innate immune cells within 24 hours 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, the neutrophils showed a distinct activation of MHC II, suggesting that neutrophils may play a more important role in antigen presentation than previously understood. 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.