title: A Single-Dose Recombinant Parainfluenza Virus 5-Vectored Vaccine Expressing Respiratory Syncytial Virus (RSV) F or G Protein Protected Cotton Rats and African Green Monkeys from RSV Challenge.
abstract: Human respiratory syncytial virus (RSV) is a common cause of severe respiratory disease among infants, immunocompromised individuals, and the elderly. No licensed vaccine is currently available. In this study, we evaluated two parainfluenza virus 5 (PIV5)-vectored vaccines expressing RSV F (PIV5/F) or G (PIV5/G) protein in the cotton rat and African green monkey models for their replication, immunogenicity, and efficacy of protection against RSV challenge. Following a single intranasal inoculation, both animal species shed the vaccine viruses for a limited time but without noticeable clinical symptoms. In cotton rats, the vaccines elicited RSV F- or G-specific serum antibodies and conferred complete lung protection against RSV challenge at doses as low as 103PFU. Neither vaccine produced the enhanced lung pathology observed in animals immunized with formalin-inactivated RSV. In African green monkeys, vaccine-induced serum and mucosal antibody responses were readily detected, as well. PIV5/F provided nearly complete protection against RSV infection in the upper and lower respiratory tract at a dose of 106PFU of vaccine. At the same dose levels, PIV5/G was less efficacious. Both PIV5/F and PIV5/G were also able to boost neutralization titers in RSV-preexposed African green monkeys. Overall, our data indicated that PIV5/F is a promising RSV vaccine candidate.IMPORTANCEA safe and efficacious respiratory syncytial virus (RSV) vaccine remains elusive. We tested the recombinant parainfluenza virus 5 (PIV5) vectors expressing RSV glycoproteins for their immunogenicity and protective efficacy in cotton rats and African green monkeys, which are among the best available animal models to study RSV infection. In both species, a single dose of intranasal immunization with PIV5-vectored vaccines was able to produce systemic and local immunity and to protect animals from RSV challenge. The vaccines could also boost RSV neutralization antibody titers in African green monkeys that had been infected previously. Our data suggest that PIV5-vectored vaccines could potentially protect both the pediatric and elderly populations and support continued development of the vector platform.
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA dai_wang@merck.com.
authors.forename: Dai
authors.identifier: http://orcid.org/0000-0001-5666-8622
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Phan
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DiStefano
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Citron
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Callahan
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Lani
authors.initials: L
authors.lastname: Indrawati
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Dubey
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Gwendolyn J
authors.initials: GJ
authors.lastname: Heidecker
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Govindarajan
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Infectious Diseases and Vaccines, Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Espeseth
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005822:Genetic Vectors; D008168:Lung / Q000821:virology; D045402:Parainfluenza Virus 5 / Q000235:genetics*; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics; D014760:Viral Fusion Proteins / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; C526850:F protein, human respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C116204:attachment protein G
keywords: PIV5 vectors; respiratory syncytial virus; vaccines