Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses

PLoS Pathog. 2024 Nov 18;20(11):e1012700. doi: 10.1371/journal.ppat.1012700. eCollection 2024 Nov.

Abstract

Alphaviruses are important arthropod-transmitted pathogens of humans and livestock. Getah virus (GETV) is an arthritogenic alphavirus that causes disease in horses and piglets; it also poses a potential threat to humans. A live attenuated vaccine candidate named GETV-3ΔS2-CM1, harbouring a deletion in nonstructural protein 3 and substitutions in the capsid protein, is genetically stable and exhibits robust immunogenicity. It was shown to confer passive protection to piglets born to immunized sows. In mice, a single dose of GETV-3ΔS2-CM1 protected against infection with different strains of GETV, Semliki Forest virus, Ross River virus, o'nyong'nyong virus, chikungunya virus, and Barmah Forest virus. Chimaeras based on the GETV-3ΔS2-CM1 backbone maintained both the attenuated phenotype and high immunogenicity. The safety, efficacy, and ability to induce protection against multiple alphaviruses highlights the potential of GETV-3ΔS2-CM1 and chimaeras using this backbone as promising vaccine candidates. By contributing simultaneously to the wellbeing of animals and humans, our universal next generation vaccine strategy helps to achieve "One Health" goals.

MeSH terms

  • Alphavirus Infections* / immunology
  • Alphavirus Infections* / prevention & control
  • Alphavirus Infections* / virology
  • Alphavirus* / genetics
  • Alphavirus* / immunology
  • Animals
  • Antibodies, Viral / immunology
  • Female
  • Horses
  • Mice
  • Swine
  • Vaccines, Attenuated* / immunology
  • Viral Vaccines* / immunology

Substances

  • Vaccines, Attenuated
  • Viral Vaccines
  • Antibodies, Viral

Grants and funding

This work was financially supported by the National Key Research and Development Program of China (grant no. 2022YFC2604203 to S.S.) and the Project of Sanya Yazhou Bay Science and Technology City (grant no. SCKJ-JYRC-2022-08 to S.S.). A.M. is the recipient of project grant (PRG1154) from Estonian Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.