Murine Pneumonia Virus Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus from an Added Gene Is Highly Attenuated and Immunogenic in Rhesus Macaques

Author:

Brock Linda G.1,Liu Xiang1,Liang Bo1,Lingemann Matthias12,Liu Xueqiao1,Herbert Richard3,Hackenberg Ashley D.3,Buchholz Ursula J.1,Collins Peter L.1,Munir Shirin1

Affiliation:

1. RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

2. Institut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany

3. Experimental Primate Virology Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Poolesville, Maryland, USA

Abstract

Human respiratory syncytial virus (RSV) is an important human pathogen that lacks a licensed vaccine or antiviral drug suitable for routine use. We describe here the evaluation of recombinant murine pneumonia virus (rMPV) as a live-attenuated vector that expresses the RSV F protein, the major RSV neutralization antigen, as an experimental RSV vaccine. The rMPV-RSV-F vectors expressing RSV F from the first, third, or fourth gene position were genetically stable and were not restricted for replication in vitro . In contrast, the vectors exhibited highly attenuated replication in the respiratory tract of rhesus macaques, maintained stable RSV F expression, and induced RSV-neutralizing serum antibodies at high titers similar to those conferred by wild-type RSV. Given the lack of preexisting immunity to MPV in humans and the lack of cross-neutralization and cross-protection between MPV and RSV, an rMPV-vectored RSV vaccine should be immunogenic in both RSV-naive children and RSV-experienced adults.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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