AS03-adjuvanted chimeric HA-based influenza vaccine induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of non-human primates

Current influenza vaccines face challenges due to antigenic evolution of the circulating virus and waning immunity in humans. Here, we investigated the durability of humoral immunity induced by an AS03-adjuvanted chimeric hemagglutinin (cHA) based influenza vaccine in non-human primates (NHPs). Two groups of NHPs (n=7 or 8) received two doses of a seasonal quadrivalent influenza vaccine (QIV) on weeks 0 and 4, followed by sequential immunization with split virus cHA vaccines cH8/1N1 (week 21), and cH5/1N1 (weeks 33 and 94). One group received cHA immunizations with AS03 adjuvant. We monitored serum antibodies and long-lived plasma cells in bone marrow for nearly 2 years after the final vaccination. The seasonal QIV vaccine induced poor HA stalk-specific antibodies and failed to give rise to detectable long-lived plasma cells in bone marrow. In contrast, cHA vaccines significantly induced stalk-specific antibody responses. Importantly, the addition of AS03 enhanced both the magnitude and durability of humoral immunity by establishing the persistence of long-lived plasma cells in the bone marrow and lymph nodes for nearly 2 years. Passive transfer of NHP serum provided protection against challenge with heterologous influenza A virus strains in mice. This study highlights the potential of the AS03-adjuvanted chimeric HA vaccine strategy to provide durable and broadly protective humoral immunity. Overall design: Ten male Rhesus macaques were innoculated with cH5/1N1, five in an un-adjuvanted group and 5 adjuvanted with AS03, following a common immunization with QIV. Blood samples were collected at Days 0, 1, 2, 4 and 7 post-innoculation for RNA-Seq analysis.