James Crowe
Faculty Member
Last active: 3/31/2020

An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats.

Mok H, Tollefson SJ, Podsiad AB, Shepherd BE, Polosukhin VV, Johnston RE, Williams JV, Crowe JE
J Virol. 2008 82 (22): 11410-8

PMID: 18786987 · PMCID: PMC2573258 · DOI:10.1128/JVI.01688-08

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.

MeSH Terms (20)

Administration, Intranasal Animals Antibodies, Viral Cell Line Encephalitis Virus, Venezuelan Equine Immunoglobulin A Immunoglobulin G Lung Macaca mulatta Metapneumovirus Mice Mice, Inbred DBA Mucous Membrane Neutralization Tests Paramyxoviridae Infections Rats Respiratory System Sigmodontinae Viral Structural Proteins Viral Vaccines

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