title: An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats.
abstract: 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.
authors.affiliation: Departments of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Hoyin
authors.initials: H
authors.lastname: Mok
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Tollefson
authors.forename: Amy B
authors.initials: AB
authors.lastname: Podsiad
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Vasiliy V
authors.initials: VV
authors.lastname: Polosukhin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnston
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D009092:Mucous Membrane / Q000276:immunology; D009500:Neutralization Tests; D018184:Paramyxoviridae Infections / Q000517:prevention & control*; D051381:Rats; D012137:Respiratory System / Q000821:virology; D016205:Sigmodontinae; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015678:Viral Structural Proteins; D014765:Viral Vaccines
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