<p>Chikungunya virus (CHIKV) causes periodic outbreaks and is endemic in more than 110 countries. VIMKUNYA, a CHIKV virus-like particle (CHIKV VLP) vaccine, was recently approved by regulators in the United States, European Union, and United Kingdom. Efficacy of VIMKUNYA in endemic settings is difficult to evaluate due to outbreak unpredictability. We used cynomolgus macaques, which model human CHIKV viremia and disease, to assess CHIKV VLP vaccine efficacy. Doses as low as 1.25 μg of CHIKV VLP with aluminum hydroxide adjuvant and passively transferred IgG from vaccinated humans significantly reduced viremia, disease, and joint pathology. Animals that received IgG doses resulting in mean reciprocal 80% neutralization titers of 35, well below the predicted protective threshold of ≥100, exhibited improved clinical outcomes compared with CHIKV-infected control animals, suggesting clinical benefits may occur at lower antibody levels. These findings demonstrate immunogenicity and protective efficacy of CHIKV VLP and relevance of neutralizing antibodies in protection, reinforcing its use in humans to protect against chikungunya disease.</p>

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A chikungunya virus-like particle vaccine reduces chikungunya disease in cynomolgus macaques and protection is mediated by antibody transferred from vaccinated humans

  • Lark L. Coffey,
  • Katherine J. Olstad,
  • J. Rachel Reader,
  • Amir Ardeshir,
  • Christopher M. Weiss,
  • Jennifer K. Watanabe,
  • Jodie L. Usachenko,
  • JoAnn Yee,
  • Anil Singapuri,
  • Zhong Min Ma,
  • Alexis Mackiewicz,
  • Rebecca Sammak,
  • Jackson Stuart,
  • Ramya Immareddy,
  • Ravi Anantha,
  • Kelly L. Warfield,
  • Darly Manayani,
  • Jeff Alexander,
  • Jonathan Smith,
  • Lo Vang,
  • Christopher M. Cirimotich,
  • Cassandra O’Connor,
  • Ben Guenther,
  • Nhuxuan Ho,
  • Christopher S. Morello,
  • Jason Mendy,
  • Jason S. Richardson,
  • Koen K. A. Van Rompay

摘要

Chikungunya virus (CHIKV) causes periodic outbreaks and is endemic in more than 110 countries. VIMKUNYA, a CHIKV virus-like particle (CHIKV VLP) vaccine, was recently approved by regulators in the United States, European Union, and United Kingdom. Efficacy of VIMKUNYA in endemic settings is difficult to evaluate due to outbreak unpredictability. We used cynomolgus macaques, which model human CHIKV viremia and disease, to assess CHIKV VLP vaccine efficacy. Doses as low as 1.25 μg of CHIKV VLP with aluminum hydroxide adjuvant and passively transferred IgG from vaccinated humans significantly reduced viremia, disease, and joint pathology. Animals that received IgG doses resulting in mean reciprocal 80% neutralization titers of 35, well below the predicted protective threshold of ≥100, exhibited improved clinical outcomes compared with CHIKV-infected control animals, suggesting clinical benefits may occur at lower antibody levels. These findings demonstrate immunogenicity and protective efficacy of CHIKV VLP and relevance of neutralizing antibodies in protection, reinforcing its use in humans to protect against chikungunya disease.