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

Pathogens

Rafael Kroon Campos¹  SashaR. Azar¹  ShannanL. Rossi²  Lorena Preciado-Llanes³  Arturo Reyes-Sandoval³  Cesar Lopez-Camacho³ 

[1] Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA;Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA;The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford OX3 7DQ, UK;

关键词: vaccine;    adenovirus-vectored;    chimpanzee adenovirus;    chikungunya virus;    alphavirus;    togaviridae;    joint swelling;    181/25;    a129 mice;   

DOI  :  10.3390/pathogens8040231

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown