The antibody landscapes against Group 1 and 2 influenza virus hemagglutinin following AS03 and MF59 adjuvanted H5N1 vaccination (probing_3_iga)

Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays (NCT01317758 and NCT01317745). The arrays were designed to reflect both full length and globular head HA derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and hetero-subtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. Adjuvanted vaccine was also associated with the elicitation of stalk directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers. We constructed two sets of influenza-specific high-density protein microarrays which comprised purified HA proteins derived from 17 influenza A virus subtypes and influenza B virus strains, including conformationally correct stabilize trimers. Our present study was designed to measure the landscape of the antibody responses in response to vaccination with an inactivated, monovalent, subvirion influenza A/Indonesia/05/2005 (H5N1) strain vaccine when administered alone (unadjuvanted) or with AS03 or MF59 adjuvant. Importantly, using stabilized trimeric headless stalk protein (HA2) in competitive inhibition assays, we indirectly assessed the elicitation of stalk-directed antibodies. Finally, the concordance between microarray subtype specific antibody levels and HAI and MN titers were evaluated.