A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

•Plant-derived virus-like particle quadrivalent influenza vaccine is safe and well-tolerated•One dose of vaccine elicits a strong, sustained and cross-reactive immune response•One dose of vaccine satisfy all CHMP surrogate correlates of protection in adults•The plant-derived vaccine induces HA-specific and cross-reactive memory CD4 T cells

Recent issues regarding efficacy of influenza vaccines have re-emphasized the need of new approaches to face this major public health issue. In a phase 1-2 clinical trial, healthy adults received one intramuscular dose of a seasonal influenza plant-based quadrivalent virus-like particle (QVLP) vaccine or placebo. The hemagglutination inhibition (HI) titers met all the European licensure criteria for the type A influenza strains at the 3 μg/strain dose and for all four strains at the higher dosages 21 days after immunization. High HI titers were maintained for most of the strains 6 months after vaccination. QVLP vaccine induced a substantial and sustained increase of hemagglutinin-specific polyfunctional CD4 T cells, mainly transitional memory and TEMRA effector IFN-γ+ CD4 T cells. A T cells cross-reactive response was also observed against A/Hong-Kong/1/1968 H3N2 and B/Massachusetts/2/2012. Plant-based QVLP offers an attractive alternative manufacturing method for producing effective and HA-strain matching seasonal influenza vaccines.