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PLoS pathogens2024; 20(11); e1012700; doi: 10.1371/journal.ppat.1012700

Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses.

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.
Copyright: © 2024 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Publication Date: 2024-11-18 PubMed ID: 39556619PubMed Central: PMC11630583DOI: 10.1371/journal.ppat.1012700Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study developed and tested an attenuated Getah virus vaccine candidate that provides protection not only against Getah virus but also against multiple related arthritogenic alphaviruses.
  • The vaccine showed safety, strong immune response, and cross-protection in animal models, indicating potential as a broad-spectrum alphavirus vaccine for both animals and humans.

Background

  • Alphaviruses are viruses transmitted by arthropods (like mosquitoes) and cause diseases in humans and livestock, often resulting in arthritis-like symptoms.
  • Getah virus (GETV) affects horses and piglets and could also infect humans, representing an emerging zoonotic threat.
  • Current vaccines for alphaviruses are limited, and there is a need for vaccines with broad protection against various alphaviruses.

Vaccine Development

  • The researchers engineered a live attenuated vaccine candidate named GETV-3ΔS2-CM1.
  • This vaccine strain has a deletion in the nonstructural protein 3 and specific mutations in the capsid protein to reduce virulence but maintain immune stimulation.
  • Genetic stability of the vaccine candidate was confirmed, ensuring that it does not revert to a harmful form.

Immunogenicity and Protection in Animals

  • The vaccine induced strong immune responses when administered to animals.
  • In piglets, passive protection was demonstrated by transfer of immunity from vaccinated sows to their offspring.
  • A single dose in mice protected against multiple alphavirus infections, including:
    • Different strains of Getah virus
    • Semliki Forest virus
    • Ross River virus
    • O’nyong’nyong virus
    • Chikungunya virus
    • Barmah Forest virus
  • This cross-protection suggests the vaccine induces broadly neutralizing immune responses against diverse alphaviruses.

Vaccine Variants and Stability

  • Chimaeras (genetically engineered viruses using the GETV-3ΔS2-CM1 backbone) were created.
  • These chimaeras retained the attenuated (weakened) phenotype, meaning they remained safe and non-virulent.
  • They also maintained high immunogenicity, confirming that the backbone can be used to develop other vaccine candidates targeting different alphaviruses.

Implications and Significance

  • The study highlights a promising next-generation vaccine strategy that targets multiple alphaviruses with one vaccine platform.
  • This approach supports the One Health concept by improving health outcomes for both animals (livestock) and humans, as alphaviruses can cross species barriers.
  • Such universal vaccines can potentially prevent outbreaks in animals and at the same time reduce the risk of human infections, addressing public health and agricultural concerns simultaneously.
  • Further development and clinical testing could lead to broadly protective alphavirus vaccines, helping control diseases caused by different arthritogenic alphaviruses worldwide.

Cite This Article

APA
Jiang Z, Merits A, Qin Y, Xing G, Zhang L, Chen J, Wang N, Varjak M, Zhai X, Li D, Song W, Su S. (2024). Attenuated Getah virus confers protection against multiple arthritogenic alphaviruses. PLoS Pathog, 20(11), e1012700. https://doi.org/10.1371/journal.ppat.1012700

Publication

PLoS pathogens
ISSN: 1553-7374
NlmUniqueID: 101238921
Country: United States
Language: English
Volume: 20
Issue: 11
Pages: e1012700
PII: e1012700

Researcher Affiliations

Jiang, Zhiwen
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Merits, Andres
  • Institute of Bioengineering, University of Tartu, Tartu, Estonia.
Qin, Ying
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Xing, Gang
  • MOA Key Laboratory of Animal Virology, Zhejiang University, Hangzhou, China.
Zhang, Letian
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Chen, Jie
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Wang, Ningning
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Varjak, Margus
  • Institute of Technology, University of Tartu, Tartu, Estonia.
Zhai, Xiaofeng
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Li, Dongyan
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Song, Wanjie
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Su, Shuo
  • Sanya Institute of Nanjing Agricultural University, Academy for Advanced Interdisciplinary Studies, Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

MeSH Terms

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

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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