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Mucosal Delivery of Recombinant Vesicular Stomatitis Virus Vectors Expressing Envelope Proteins of Respiratory Syncytial Virus Induces Protective Immunity in Cotton Rats.
- Source :
-
Journal of virology [J Virol] 2021 Feb 24; Vol. 95 (6). Date of Electronic Publication: 2021 Feb 24 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract (LRT) infections, with increased severity in high-risk human populations, such as infants, the immunocompromised, and the elderly. Although the virus was identified more than 60 years ago, there is still no licensed vaccine available. Over the years, several vaccine delivery strategies have been evaluated. In this study, we developed two recombinant vesicular stomatitis virus (rVSV) vector-based vaccine candidates expressing the RSV-G (attachment) protein (rVSV-G) or F (fusion) protein (rVSV-F). All vectors were evaluated in the cotton rat animal model for their in vivo immunogenicity and protective efficacy against an RSV-A2 virus challenge. Intranasal (i.n.) delivery of rVSV-G and rVSV-F together completely protected the lower respiratory tract (lungs) at doses as low as 10 <superscript>3</superscript> PFU. In contrast, doses greater than 10 <superscript>6</superscript> PFU were required to protect the upper respiratory tract (URT) completely. Reimmunization of RSV-immune cotton rats was most effective with rVSV-F. In immunized animals, overall antibody responses were sufficient for protection, whereas CD4 and CD8 T cells were not necessary. A prime-boost immunization regimen increased both protection and neutralizing antibody titers. Overall, mucosally delivered rVSV-vector-based RSV vaccine candidates induce protective immunity and therefore represent a promising immunization regimen against RSV infection. IMPORTANCE Even after decades of intensive research efforts, a safe and efficacious RSV vaccine remains elusive. Expression of heterologous antigens from rVSV vectors has demonstrated several practical and safety advantages over other virus vector systems and live attenuated vaccines. In this study, we developed safe and efficacious vaccine candidates by expressing the two major immunogenic RSV surface proteins in rVSV vectors and delivering them mucosally in a prime-boost regimen. The main immune parameter responsible for protection was the antibody response. These vaccine candidates induced complete protection of both the upper and lower respiratory tracts.<br /> (Copyright © 2021 American Society for Microbiology.)
- Subjects :
- Administration, Mucosal
Animals
Disease Models, Animal
Genetic Vectors
Immunity, Cellular
Immunity, Humoral
Immunization
Recombinant Proteins genetics
Recombinant Proteins immunology
Recombinant Proteins metabolism
Respiratory Syncytial Virus Infections immunology
Respiratory Syncytial Virus Vaccines immunology
Respiratory Syncytial Virus, Human genetics
Respiratory System immunology
Respiratory System virology
Sigmodontinae
Vaccines, Attenuated administration & dosage
Vaccines, Attenuated immunology
Vesiculovirus metabolism
Viral Envelope Proteins genetics
Viral Envelope Proteins metabolism
Viral Fusion Proteins genetics
Viral Fusion Proteins metabolism
Respiratory Syncytial Virus Infections prevention & control
Respiratory Syncytial Virus Vaccines administration & dosage
Respiratory Syncytial Virus, Human immunology
Vesiculovirus genetics
Viral Envelope Proteins immunology
Viral Fusion Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 95
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 33408176
- Full Text :
- https://doi.org/10.1128/JVI.02345-20