title: Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates.
abstract: Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Bates
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Pickens
authors.affiliation: The Department of Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Schuster
authors.affiliation: The Department of Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Johnson
authors.affiliation: The Department of Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Tollefson
authors.affiliation: The Department of Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.affiliation: The Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Davis
authors.affiliation: Global Vaccines, Research Triangle Park, Durham, NC 27709, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnston
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Schultz-Darken
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Department of Biostatistics of Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Smith-House
authors.affiliation: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Department of Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000524:Alphavirus; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D002522:Chlorocebus aethiops; D004666:Encephalitis Virus, Venezuelan Equine; D007074:Immunoglobulin G / Q000097:blood; D029121:Metapneumovirus; D009500:Neutralization Tests; D009666:Nose / Q000821:virology; D018184:Paramyxoviridae Infections / Q000517:prevention & control*; D012093:Replicon; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human; D014760:Viral Fusion Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D007074:Immunoglobulin G; D014760:Viral Fusion Proteins; D014765:Viral Vaccines
keywords: Metapneumovirus; Nonhuman primates; Replicon particles; Respiratory syncytial virus; Vaccine