VACCINATION WITH A RECOMBINANT VESICULAR STOMATITIS-VIRUS EXPRESSING AN INFLUENZA-VIRUS HEMAGGLUTININ PROVIDES COMPLETE PROTECTION FROM INFLUENZA-VIRUS CHALLENGE

Since the development of a system for generating vesicular stomatitis virus (VSV) from plasmid DNAs, our laboratory has reported the express ion of several different glycoproteins from recombinant VSVs. In one o f these studies, high-level expression of an influenza virus hemagglut inin (HA) from a recombinant VSV-HA and efficient incorporation of the BA protein into the virions was reported (E. Kretzschmar, L. Buonocor e, M. J. Schnell, and J. K. Rose, J. Virol. 71:5982-5989, 1997). We re port here that VSV-HA is an effective intranasal vaccine vector that r aises high levels of neutralizing antibody to influenza virus and comp letely protects mice from bronchial pneumonia caused by challenge with a lethal dose of influenza A virus. Additionally, these recombinant V SVs are less pathogenic than wild-type VSV (serotype Indiana). This ve ctor-associated pathogenicity was subsequently eliminated through intr oduction of specific attenuating deletions. These live attenuated reco mbinant VSVs have great potential as vaccine vectors.