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Clinical and Vaccine Immunology, April 2009, p. 488-498, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00451-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Recombinant Vesicular Stomatitis Virus Expressing Influenza Nucleoprotein Induces CD8 T-Cell Responses That Enhance Antibody-Mediated Protection after Lethal Challenge with Influenza Virus{triangledown}

Brice E. Barefoot, Christopher J. Sample, and Elizabeth A. Ramsburg*

Duke University Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710

Received 2 December 2008/ Returned for modification 26 January 2009/ Accepted 15 February 2009

Live attenuated vaccine vectors based on recombinant vesicular stomatitis viruses (rVSVs) expressing foreign antigens are highly effective vaccines in animal models. In this study, we report that an rVSV expressing influenza nucleoprotein (VSV NP) from the first position of the VSV genome induces robust anti-NP CD8 T cells in immunized mice. These CD8 T cells are phenotypically similar to those induced by natural influenza infection and are cytotoxic in vivo. Animals immunized with an rVSV expressing the influenza hemagglutinin (rVSV HA) were protected but still exhibited considerable morbidity after challenge. Animals receiving a cocktail vaccine of rVSV NP and rVSV HA had reduced pulmonary viral loads, less weight loss, and reduced clinical signs of illness after influenza virus challenge, relative to those vaccinated with rVSV HA alone. Influenza NP is a highly conserved antigen, and induction of protective anti-NP responses may be a productive strategy for generating heterologous protection against divergent influenza strains.

* Corresponding author. Mailing address: Duke University Medical Center, Global Health Research Building, Room 1044, 102 Research Drive, Durham, NC 27710. Phone: (919) 684-8183. Fax: (919) 681-1678. E-mail: elizabeth.ramsburg{at}duke.edu

{triangledown} Published ahead of print on 25 February 2009.

Clinical and Vaccine Immunology, April 2009, p. 488-498, Vol. 16, No. 4
1071-412X/09/$08.00+0     doi:10.1128/CVI.00451-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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