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Journal of Virology, November 2008, p. 11410-11418, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01688-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

An Alphavirus Replicon-Based Human Metapneumovirus Vaccine Is Immunogenic and Protective in Mice and Cotton Rats{triangledown}

Hoyin Mok,1,5 Sharon J. Tollefson,1 Amy B. Podsiad,1 Bryan E. Shepherd,3 Vasiliy V. Polosukhin,4 Robert E. Johnston,6 John V. Williams,1,2 and James E. Crowe Jr1,2,5*

Departments of Pediatrics,1 Microbiology and Immunology,2 Biostatistics,3 Medicine,4 The Program for Vaccine Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232,5 Carolina Vaccine Institute and Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 275996

Received 7 August 2008/ Accepted 2 September 2008

Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.

* Corresponding author. Mailing address: T-2220 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232-2905. Phone: (615) 343-8064. Fax: (615) 343-4456. E-mail: james.crowe{at}vanderbilt.edu

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 11410-11418, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01688-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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