A Single Dose TMV-HA Vaccine Protects Mice from H5N1 Influenza Challenge

Abstract

Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant Hemagglutinin (HA) subunit protein are often of low potency, requiring repeated boosting to generate a sustained immune response. Previously, we demonstrated improved immunogenicity of a plant-made H1 Hemagglutinin (HA) vaccine by chemical conjugation to the surface of the Tobacco Mosaic Virus (TMV) which is non infectious in mammals. Antigen coated TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier for subunit protein vaccines. In this work, we tested the effectiveness of a TMV-H5 HA conjugate vaccine. We compared the TMV-H5 immunogenicity in mice, with and without an oil-in water squalene adjuvant, to H5N1 virus or HA protein alone, as measured by anti-H5 IgG titers and Hemagglutination Inhibition (HAI). We then evaluated the efficacy of the TMV-H5 vaccine by lethal H5N1 virus challenge in mice. Our results show that a single dose of the TMV-H5 conjugate vaccine is sufficient to generate 40% survival, similar to H5 protein given with adjuvant, or 100% survival after vaccination with adjuvant, similar to H5N1 virus vaccination.