A live single-cycle RSV vaccine expressing prefusion F protein

Virology. 2022 Dec:577:51-64. doi: 10.1016/j.virol.2022.10.003. Epub 2022 Oct 15.


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.

Keywords: Fusion protein; GP64; Prefusion F; Respiratory syncytial virus; Vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Mice
  • Respiratory Syncytial Virus Infections*
  • Respiratory Syncytial Virus Vaccines* / genetics
  • Respiratory Syncytial Virus, Human* / genetics
  • Viral Fusion Proteins / genetics


  • Respiratory Syncytial Virus Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Viral Fusion Proteins