cross-clade protective immune responses to influenza viruses with h5n1 ha and na elicited by an influenza virus-like particlecross-clade保护性免疫反应与h5n1流感病毒血凝素和神经氨酸酶引起的流感病毒样颗粒.pdfVIP

Cross-Clade Protective Immune Responses to Influenza Viruses with H5N1 HA and NA Elicited by an Influenza Virus-Like Particle 1 2 2 2 2 2 1 Rick A. Bright *, Donald M. Carter , Corey J. Crevar , Franklin R. Toapanta , Jonathan D. Steckbeck , Kelly S. Cole , Niranjan M. Kumar , Peter 1 1 3 2 Pushko , Gale Smith , Terrence M. Tumpey , Ted M. Ross * 1 Novavax, Inc., Rockville, Maryland, United States of America, 2 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America Background. Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine. Methodology/Principal Findings. We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential. VLPs were administered to mice in either a one-dose or two-dose regimen and the immune responses were compared to those induced by recombinant hemagglutinin (rHA). Both humoral and cellular responses were analyzed. Mice vaccinated with VLPs were protected against challenge with lethal reassortant viruses expressing the H5N1 HA and NA, regardless if the H5N1 clade was homologous or heterologous to the vaccine. However, rHA-vaccinated mice showed considera