A single and un-adjuvanted dose of a chimpanzee adenovirus-vectored vaccine against chikungunya virus fully protects mice from lethal disease

Rafael Kroon Campos, Lorena Preciado-Llanes, Sasha R. Azar, Cesar Lopez-Camacho, Arturo Reyes-Sandoval, Shannan L. Rossi

Research output: Contribution to journalArticle

Abstract

The mosquito-borne chikungunya virus (CHIKV) has become a major global health problem. Upon infection, chikungunya fever (CHIKF) can result in long-term joint pain and arthritis, and despite intense research, no licensed vaccine for CHIKV is available. We have developed two recombinant chimpanzee adenovirus-vectored vaccines (ChAdOx1) that induce swift and robust anti-CHIKV immune responses with a single dose, without the need for adjuvants or booster vaccines. Here, we report the vaccines’ protective efficacies against CHIKV infection in a lethal A129 mouse model. Our results indicate that a single, un-adjuvanted ChAdOx1 Chik or ChAdOx1 Chik ∆Cap dose provided complete protection against a lethal virus challenge and prevented CHIKV-associated severe inflammation. These candidate vaccines supported survival equal to the attenuated 181/25 CHIKV reference vaccine but without the vaccine-related side effects, such as weight loss. Vaccination with either ChAdOx1 Chik or ChAdOx1 Chik ∆Cap resulted in high titers of neutralizing antibodies that are associated with protection, indicating that the presence of the capsid within the vaccine construct may not be essential to afford protection under the conditions tested. We conclude that both replication-deficient ChAdOx1 Chik vaccines are safe even when used in A129 mice and afford complete protection from a lethal challenge.

Original languageEnglish (US)
Article number231
JournalPathogens
Volume8
Issue number4
DOIs
StatePublished - Dec 2019

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Adenovirus Vaccines
Chikungunya virus
Pan troglodytes
Vaccines
Capsid
Arthralgia
Neutralizing Antibodies
Culicidae
Arthritis
Weight Loss
Vaccination
Viruses
Inflammation

Keywords

  • 181/25
  • A129 mice
  • Adenovirus-vectored
  • Alphavirus
  • Chikungunya virus
  • Chimpanzee adenovirus
  • Joint swelling
  • Togaviridae
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

Cite this

A single and un-adjuvanted dose of a chimpanzee adenovirus-vectored vaccine against chikungunya virus fully protects mice from lethal disease. / Campos, Rafael Kroon; Preciado-Llanes, Lorena; Azar, Sasha R.; Lopez-Camacho, Cesar; Reyes-Sandoval, Arturo; Rossi, Shannan L.

In: Pathogens, Vol. 8, No. 4, 231, 12.2019.

Research output: Contribution to journalArticle

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