A live single-cycle RSV vaccine expressing prefusion F protein

Pramila Lamichhane; Megan E. Schmidt; Megolhubino Terhüja; Steven M. Varga; Timothy A. Snider; Christina A. Rostad; Antonius G.P. Oomens

doi:10.1016/j.virol.2022.10.003

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A live single-cycle RSV vaccine expressing prefusion F protein

Journal article

Open access

Peer reviewed

A live single-cycle RSV vaccine expressing prefusion F protein

Pramila Lamichhane, Megan E. Schmidt, Megolhubino Terhüja, Steven M. Varga, Timothy A. Snider, Christina A. Rostad and Antonius G.P. Oomens

Virology (New York, N.Y.), Vol.577, pp.51-64

12/2022

DOI: 10.1016/j.virol.2022.10.003

PMCID: PMC10104964

PMID: 36306605

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Abstract

Live-attenuated Respiratory syncytial virus (RSV) vaccines given intranasally have potential to provide comprehensive protection, including lung-resident immunity. It has however proven challenging to impart both sufficient safety and efficacy in a vaccine. To achieve the latter, we used a trans-complementing approach to generate live single-cycle RSV vaccines expressing the prefusion form (preF) of the viral fusion protein (F), either membrane-anchored or secreted. Both viruses were tested for their ability to induce a protective immune response in mice after intranasal prime-boost vaccination. The secreted preF vaccine failed to induce a protective response. The anchored preF vaccine induced anti-preF antibodies and antiviral T cells, and protected mice from lung pathology and viral shedding after challenge. Neither vaccine induced anti-G antibodies, for reasons unknown. In spite of the latter and single-cycle replication, the membrane-anchored preF vaccine was protective and demonstrates potential for development of an efficacious live vaccine with a stable safety phenotype. •Vaccine single-cycle replication combines safety and broad efficacy.•A single-cycle RSV vaccine induces antibodies and T cells and protects from challenge.•Exclusive expression of prefusion F increases the ratio of preF:postF antibodies.•Anti-viral T cells alone may not be sufficient to protect from RSV lung pathology.

Fusion protein

GP64

Prefusion F

Respiratory syncytial virus

Vaccine

Details

Title: Subtitle: A live single-cycle RSV vaccine expressing prefusion F protein
Creators: Pramila Lamichhane - Oklahoma State University
Megan E. Schmidt - University of Iowa
Megolhubino Terhüja - Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, 74078, USA
Steven M. Varga - University of Iowa
Timothy A. Snider - Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK, 74078, USA
Christina A. Rostad - Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA
Antonius G.P. Oomens - Oklahoma State University
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.577, pp.51-64
DOI: 10.1016/j.virol.2022.10.003
PMID: 36306605
PMCID: PMC10104964
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100008562, name: University of Texas at Austin; DOI: 10.13039/100000002, name: National Institutes of Health, award: R21AI128520; DOI: 10.13039/100008788, name: College of Veterinary Medicine, Ohio State University; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: P20GM103648; DOI: 10.13039/100006492, name: Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Language: English
Date published: 12/2022
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Community and Behavioral Health
Record Identifier: 9984311459502771

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