Probing the attenuation and protective efficacy of a c-idate Chikungunya virus vaccine in mice with compromised interferon (IFN) signaling
Autor(es): Partidos Charalambos D, Weger James, Brewoo Joseph, Seymour Robert, Borland Erin M, Ledermann Jeremy P, Powers Ann M, Weaver Scott C, Stinchcomb Dan T, Osorio Jorge E
Resumo: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes explosive outbreaks of febrile illness associated with rash, - painful arthralgia. The CHIK vaccine strain 181/clone25 (181/25) developed by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) was shown to be well-tolerated - highly immunogenic in phase I - II clinical trials although it induced transient arthralgia in some healthy adult volunteers. In an attempt to better underst- the host factors that are involved in the attenuating phenotype of CHIK 181/25 vaccine virus we conducted studies in interferon (IFN)-compromised mice - also evaluated its immunogenic potential - protective capacity. Infection of AG129 mice (defective in IFN-?/? - IFN-? receptor signaling) with CHIK 181/25 resulted in rapid mortality within 3-4 days. In contrast, all infected A129 mice (defective in IFN-?/? receptor signaling) survived with temporary morbidity characterized by ruffled appearance - body weight loss. A129 heterozygote mice that retain partial IFN-?/? receptor signaling activity remained healthy. Infection of A129 mice with CHIK 181/25 induced significant levels of IFN-? - IL-12 while the inflammatory cytokines, TNF? - IL-6 remained low. A single administration of the CHIK 181/25 vaccine provided both short-term - long-term protection (38 days - 247 days post-prime, respectively) against challenge with wt CHIKV-La Reunion (CHIKV-LR). This protection was at least partially mediated by antibodies since passively transferred immune serum protected both A129 - AG129 mice from wt CHIKV-LR - 181/25 virus challenge. Overall, these data highlight the importance of IFNs in controlling CHIK 181/25 vaccine - demonstrate the ability of this vaccine to elicit neutralizing antibody responses that confer short-- long-term protection against wt CHIKV-LR challenge.
Palavras-Chave: Chikungunya virus (CHIKV); 181/25 vaccine; A129 mice; Interferon
Imprenta: Vaccine, v. 29, n. 16, p. 3067-3073, 2011
Identificador do objeto digital: 10.1016/j.vaccine.2011.01.076
Descritores: Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Cytokines ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Inflammation ; Chikungunya virus - Serology ; Chikungunya virus - Viral infections ; Chikungunya virus - Serology ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Immunology
Data de publicação: 2011
