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Open AccessArticle

A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease

1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
2
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7DQ, UK
3
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Authors to whom correspondence should be addressed.
Authors contributed equally.
Pathogens 2019, 8(4), 231; https://doi.org/10.3390/pathogens8040231
Received: 15 October 2019 / Revised: 7 November 2019 / Accepted: 8 November 2019 / Published: 12 November 2019
(This article belongs to the Special Issue Vaccines against Alphaviruses and Flaviviruses)
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 ΔCap 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 ΔCap 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. View Full-Text
Keywords: vaccine; adenovirus-vectored; chimpanzee adenovirus; chikungunya virus; alphavirus; Togaviridae; joint swelling; 181/25; A129 mice vaccine; adenovirus-vectored; chimpanzee adenovirus; chikungunya virus; alphavirus; Togaviridae; joint swelling; 181/25; A129 mice
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Campos, R.K.; Preciado-Llanes, L.; Azar, S.R.; Lopez-Camacho, C.; Reyes-Sandoval, A.; Rossi, S.L. A Single and Un-Adjuvanted Dose of a Chimpanzee Adenovirus-Vectored Vaccine against Chikungunya Virus Fully Protects Mice from Lethal Disease. Pathogens 2019, 8, 231.

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