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An intranasal attenuated Coxsackievirus B3 vaccine induces strong systemic and mucosal immunity against CVB3 lethal challenge
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  • Huixiong Deng,
  • Yanlei Li,
  • Xuanting He,
  • Haoyang Wang,
  • Shenmiao Wang,
  • Hengyao Zhang,
  • Jiacheng Zhu,
  • Liming Gu,
  • Rui Li,
  • Gefei Wang
Huixiong Deng
Shantou University
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Yanlei Li
Shantou University
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Xuanting He
Shantou University
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Haoyang Wang
Shantou University
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Shenmiao Wang
Shantou University
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Hengyao Zhang
Shantou University
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Jiacheng Zhu
Shantou University
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Liming Gu
Shantou University
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Rui Li
Shantou University
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Gefei Wang
Shantou University

Corresponding Author:[email protected]

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Abstract

Coxsackievirus B3 (CVB3) triggers viral myocarditis, with no effective vaccine yet. This fecal-orally transmitted pathogen has prompted interest in mucosal immunization to impede CVB3 spread. Our lab identified an attenuated strain, CVB3(mu), offering myocarditis and pancreatitis protection against CVB3(WT) in susceptible Balb/c mice. CVB3(mu)’s potential to stimulate mucosal immune defense remains to be elucidated. This study evaluates CVB3(mu)’s genetic stability via a rapid evolution cellular model and RNA sequencing. Its temperature sensitivity and safety were evaluated through in vitro and in vivo experiments. CVB3(mu)’s mucosal immunity protection was assessed via intranasal immunization in Balb/c mice. Results show CVB3(mu) maintains genetic stability and temperature sensitivity, retaining attenuated traits up to the 25th passage. Intranasal immunization elicited a significant Th1 response, potent serum neutralizing antibodies, and a substantial sIgA response in nasal washes. In vivo trials revealed CVB3(mu) protection in adult mice and passive protection in suckling mice against lethal CVB3(WT) challenges. In conclusion, CVB3(mu), a live attenuated intranasal vaccine, provides tripartite protection involving humoral, mucosal, and cellular immunity, making it a potential candidate to control CVB3 spread and infection.
21 Apr 2024Submitted to Journal of Medical Virology
26 Apr 2024Reviewer(s) Assigned
06 Jun 2024Submission Checks Completed
06 Jun 2024Assigned to Editor
06 Jun 2024Review(s) Completed, Editorial Evaluation Pending
26 Jun 2024Submission Checks Completed
26 Jun 2024Assigned to Editor
26 Jun 2024Review(s) Completed, Editorial Evaluation Pending
17 Jul 2024Editorial Decision: Accept