1887

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Volume 104, Issue 6

Production of antigenically stable enterovirus A71 virus-like particles in as a vaccine candidate Open Access

Abstract

Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation.

We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in .

The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus . Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): EVA71 , hand, foot and mouth disease, virus-like particle , vaccine and VLP
Funding
This study was supported by the:
  • Leverhulme Trust (Award x)
    • Principle Award Recipient: JamesM. Hogle
  • Wellcome Trust (Award 102174/B/13/Z)
    • Principle Award Recipient: JosephS Snowden
  • Wellcome Trust (Award 204825/Z/16/Z)
    • Principle Award Recipient: NatalieJ Kingston
  • Wellcome Trust (Award 204825/Z/16/Z)
    • Principle Award Recipient: KeithGrehan
  • Medical Research Council (Award MR/P022626/1)
    • Principle Award Recipient: NicolaJ Stonehouse
  • Medical Research Council (Award MR/P022626/1)
    • Principle Award Recipient: AndrewJ Macadam
  • Medical Research Council (Award MR/P022626/1)
    • Principle Award Recipient: DavidRowlands
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-06-30
2024-05-08
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Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate
J. Gen. Virol. 104, 001867 (2023); https://doi.org/10.1099/jgv.0.001867
/content/journal/jgv/10.1099/jgv.0.001867
/content/journal/jgv/10.1099/jgv.0.001867
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