Deciphering the protective role of adaptive immunity to CHIKV/IRES a novel candidate vaccine against Chikungunya in the A129 mouse model
Autor(es): Chu Haiyan, Das Subash C, Fuchs Jeremy F, Suresh M, Weaver Scott C, Stinchcomb Dan T, Partidos Charalambos D, Osorio Jorge E
Resumo: Chikungunya virus (CHIKV), a mosquito-borne alphavirus, recently re-emerged in Africa - spread to isl-s in the Indian Ocean, the Indian subcontinent, - to South East Asia. Viremic travelers have also imported CHIKV to the Western hemisphere highlighting the importance of CHIKV in public health. In addition to the great burden of arthralgic disease, which can persist for months or years, epidemiologic studies have estimated case-fatality rates of ?0.1%, principally from neurologic disease in older patients. There are no licensed vaccines or effective therapies to prevent or treat human CHIKV infections. We have developed a live CHIKV vaccine (CHIKV/IRES) that is highly attenuated yet immunogenic in mouse models, - is incapable of replicating in mosquito cells. In this study we sought to decipher the role of adaptive immunity elicited by CHIKV/IRES in protection against wild-type CHIKV infection. A single dose of vaccine effectively activated T cells with an expansion peak on day 10 post immunization - elicited memory CD4(+) - CD8(+) T cells that produced IFN-?, TNF-? - IL-2 upon restimulation with CHIKV/IRES. Adoptive transfer of CHIKV/IRES-immune CD4(+) or CD8(+) T cells did not confer protection against wtCHIKV-LR challenge. By contrast, passive immunization with anti-CHIKV/IRES immune serum provided protection, - a correlate of a minimum protective neutralizing antibody titer was established. Overall, our findings demonstrate the immunogenic potential of the CHIKV/IRES vaccine - highlight the important role that neutralizing antibodies play in protection against an acute CHIKV infection.
Palavras-Chave: A129 mice; Cellular immunity; Chikungunya (CHIKV); Humoral immunity; Interferon (IFN); Protection
Imprenta: Vaccine, v. 31, n. 33, p. 3353-3360, 2013
Identificador do objeto digital: 10.1016/j.vaccine.2013.05.059
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - T lymphocytes ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2013
