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 expression of several different glycoproteins from recombinant VSVs. In one of these studies, high-level expression of an influenza virus hemagglutinin (HA) from a recombinant VSV-HA and efficient incorporation of the HA protein into the virions was reported (E. Kretzschmar, L. Buonocore, M. J. Schnell, and J. K. Rose, J. Virol. 71:5982-5989, 1997). We report here that VSV-HA is an effective intranasal vaccine vector that raises high levels of neutralizing antibody to influenza virus and completely protects mice from bronchial pneumonia caused by challenge with a lethal dose of influenza A virus. Additionally, these recombinant VSVs are less pathogenic than wild-type VSV (serotype Indiana). This vector-associated pathogenicity was subsequently eliminated through introduction of specific attenuating deletions. These live attenuated recombinant VSVs have great potential as vaccine vectors.
Roberts
A
A
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Kretzschmar
E
E
Perkins
A S
AS
Forman
J
J
Price
R
R
Buonocore
L
L
Kawaoka
Y
Y
Rose
J K
JK
D000280:Administration, Inhalation; D000818:Animals; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology*; D007109:Immunity; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D004274:DNA, Recombinant; D006388:Hemagglutinins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines