A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial

• Published in: Nature communications Vol. 12; no. 1; p. 4636
• Main Authors: Folegatti, Pedro M., Harrison, Kate, Preciado-Llanes, Lorena, Lopez, Fernando Ramos, Bittaye, Mustapha, Kim, Young Chan, Flaxman, Amy, Bellamy, Duncan, Makinson, Rebecca, Sheridan, Jonathan, Azar, Sasha R., Campos, Rafael Kroon, Tilley, Mark, Tran, Nguyen, Jenkin, Daniel, Poulton, Ian, Lawrie, Alison, Roberts, Rachel, Berrie, Eleanor, Rossi, Shannan L., Hill, Adrian, Ewer, Katie J., Reyes-Sandoval, Arturo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 13/44; 631/250/590; 631/326/596/1282; 692/308/409; 692/699/255/2514; Adenoviruses; Adverse events; Antibodies; Antigens; Chikungunya virus; Dosage; Humanities and Social Sciences; Immunogenicity; Immunoglobulin G; Lymphocytes T; Mosquitoes; multidisciplinary; Neutralizing; Outbreaks; Safety; Science; Science (multidisciplinary); Seroconversion; Vaccination; Vaccines; Vector-borne diseases; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24906-y

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT 50 seroconversion after a single dose. Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.