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J. Virol. doi:10.1128/JVI.00844-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Human Metapneumovirus Fusion Protein Vaccines that are Immunogenic and Protective in Cotton Rats

Departments of Chemistry, Pediatrics, Pathology and Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN

^* To whom correspondence should be addressed. Email: john.williams{at}vanderbilt.edu.

	Abstract

Human metapneumovirus (hMPV) is a recently described paramyxovirus that is a major cause of upper and lower respiratory infection in children and adults worldwide. A safe and effective vaccine could decrease the burden of disease associated with this novel pathogen. We previously reported the development of the cotton rat model of hMPV infection and pathogenesis (Williams JV, Tollefson SJ, Johnson JE, Crowe JE Jr. Journal of Virology 2005;79(17):10944-51.). Here, we report the immunogenicity of an hMPV fusion (F) protein in this model. We constructed DNA plasmids that exhibited high levels of expression of hMPV F in mammalian cells (DNA-F). These constructs were used to develop a novel strategy to produce highly pure, soluble hMPV F protein lacking the transmembrane domain (FTM). We then immunized cotton rats at 0 and 14 days with either control vector, DNA-F alone, DNA-F followed by FTM protein, or FTM alone. All groups were challenged intranasally at 28 days with live hMPV. All 3 groups that received some form of hMPV F immunization mounted neutralizing antibody responses and exhibited partial protection against virus shedding in the lungs compared to controls. The FTM-immunized animals showed the greatest degree of protection (>1500-fold reduction in lung virus titer). All 3 immunized groups showed a modest reduction of nasal virus shedding. Neither evidence of a Th2-type response nor increased lung pathology were present in the immunized animals. We conclude that sequence-optimized hMPV F protein protects against hMPV infection when delivered as either a DNA or protein vaccine in cotton rats.

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