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Vaccine2011; 29(34); 5623-5630; doi: 10.1016/j.vaccine.2011.06.015

A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

Abstract: The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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Publication Date: 2011-07-01 PubMed ID: 21689706PubMed Central: PMC3153950DOI: 10.1016/j.vaccine.2011.06.015Google 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.

This research presents the development of a vaccine to combat the deadly Hendra virus (HeV) in ferrets, a virus equally harmful to humans and horses. Using different doses of the HeV G glycoprotein-based vaccine, the study shows promising results in preventing HeV infection and virus shedding in ferrets.

Understanding the Hendra Virus (HeV)

  • In the family of henipaviruses, Hendra virus and Nipah virus are two pathogens that cause fatal infections in humans and livestock.
  • Since its discovery in 1994, 14 outbreaks of HeV have occurred resulting in many fatalities in horses and humans. Human infections are known to result from close contact with infected horses.
  • Therefore, creating a vaccine to prevent virus contamination in horses can help the transmission chain to humans, safeguarding both species from HeV disease.

Research Approach and Findings

  • The research utilized a ferret model to study HeV infection in depth, finding that it closely resonates with diseases visible in humans and horses.
  • Particularly, it was found that HeV induces systemic vasculitis and impacts both the pulmonary and central nervous systems.
  • A subunit vaccine, based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), was developed and adjuvanted with CpG (a popular adjuvant for vaccines).
  • Vaccinated ferrets with doses of 100 μg, 20 μg or 4 μg of HeVsG displayed no clinical signs of HeV infection after being exposed to 5000 TCID₅₀ of HeV, a large amount of the virus signifying the robustness of the vaccine.
  • To assess the vaccine’s effectiveness, the researchers looked for evidence of the virus or viral genome in all tissues or body fluids. They found none in the 100 and 20 μg groups, while the virus genome was detected only in the nasal washes of one animal in the 4 μg group.

Conclusion and Implications

  • These results suggest that the HeVsG vaccine can entirely prevent a productive HeV infection in ferrets, particularly when applied in 100 μg or 20 μg doses.
  • This study’s findings provide significant evidence that creating a vaccine to prevent HeV infection and shedding is achievable, which could potentially interrupt the transmission from horses to humans.
  • While the research was conducted in a ferret model, the translation of these findings to horse and human applications will be an essential follow-up study.

Cite This Article

APA
Pallister J, Middleton D, Wang LF, Klein R, Haining J, Robinson R, Yamada M, White J, Payne J, Feng YR, Chan YP, Broder CC. (2011). A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge. Vaccine, 29(34), 5623-5630. https://doi.org/10.1016/j.vaccine.2011.06.015

Publication

Vaccine
ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 29
Issue: 34
Pages: 5623-5630

Researcher Affiliations

Pallister, Jackie
  • CSIRO Livestock Industries, Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia. jackie.pallister@csiro.au
Middleton, Deborah
    Wang, Lin-Fa
      Klein, Reuben
        Haining, Jessica
          Robinson, Rachel
            Yamada, Manabu
              White, John
                Payne, Jean
                  Feng, Yan-Ru
                    Chan, Yee-Peng
                      Broder, Christopher C

                        MeSH Terms

                        • Animals
                        • Antibodies, Viral / immunology
                        • Ferrets / immunology
                        • Ferrets / virology
                        • Glycoproteins / immunology
                        • Hendra Virus / immunology
                        • Henipavirus Infections / immunology
                        • Henipavirus Infections / prevention & control
                        • Recombinant Proteins / immunology
                        • Vaccines, Subunit / immunology
                        • Vaccines, Synthetic / immunology
                        • Viral Envelope Proteins / immunology
                        • Viral Vaccines / immunology
                        • Virus Shedding / immunology

                        Grant Funding

                        • R01 AI054715 / NIAID NIH HHS
                        • U01 AI077995 / NIAID NIH HHS
                        • AI077995 / NIAID NIH HHS
                        • AI054715 / NIAID NIH HHS

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