Improved adjuvanting of seasonal influenza vaccines: Pre-clinical studies of MVA-NP+M1 co-administration with inactivated influenza vaccine.

Licensed seasonal influenza vaccines induce antibody responses against influenza hemagglutinin that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes (CTLs) recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia virus Ankara encoding NP and M1 (MVA-NP+M1) is designed to boost pre-existing T-cell responses in adults in order to elicit a cross-protective immune response. We examined the co-administration of hemagglutinin (HA) protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Antibody responses post-immunization were measured by ELISA and pseudotype neutralization assays. Here we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing antibody (Ab) responses to HA while simultaneously inducing potent T-cell responses to conserved internal antigens. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and antibody responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations.