Prime-boost immunization strategies against Chikungunya virus
Autor(es): Hallengärd David, Lum Fok-Moon, Kümmerer Beate M, Lulla Aleksei, Lulla Valeria, García-Arriaza Juan, Fazakerley John K, Roques Pierre, Le Grand Roger, Merits Andres, Ng Lisa F P, Esteban Mariano, Liljeström Peter
Resumo: Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that causes debilitating arthralgia in humans. Here we describe the development - testing of novel DNA replicon - protein CHIKV vaccine c-idates - evaluate their abilities to induce antigen-specific immune responses against CHIKV. We also describe homologous - heterologous prime-boost immunization strategies using novel - previously developed CHIKV vaccine c-idates. Immunogenicity - efficacy were studied in a mouse model of CHIKV infection - showed that the DNA replicon - protein antigen were potent vaccine c-idates, particularly when used for priming - boosting, respectively. Several prime-boost immunization strategies eliciting unmatched humoral - cellular immune responses were identified. Further characterization by antibody epitope mapping revealed differences in the qualitative immune responses induced by the different vaccine c-idates - immunization strategies. Most vaccine modalities resulted in complete protection against wild-type CHIKV infection; however, we did identify circumstances under which certain immunization regimens may lead to enhancement of inflammation upon challenge. These results should help guide the design of CHIKV vaccine studies - will form the basis for further preclinical - clinical evaluation of these vaccine c-idates. As of today, there is no licensed vaccine to prevent CHIKV infection. In considering potential new vaccine c-idates, a vaccine that could raise long-term protective immunity after a single immunization would be preferable. While humoral immunity seems to be central for protection against CHIKV infection, we do not yet fully underst- the correlates of protection. Therefore, in the absence of a functional vaccine, there is a need to evaluate a number of different c-idates, assessing their merits when they are used either in a single immunization or in a homologous or heterologous prime-boost modality. Here we show that while single immunization with various vaccine c-idates results in potent responses, combined approaches significantly enhance responses, suggesting that such approaches need to be considered in the further development of an efficacious CHIKV vaccine.
Imprenta: Journal of Virology, v. 88, n. 22, p. 13333-13343, 2014
Identificador do objeto digital: 10.1128/JVI.01926-14
Descritores: Chikungunya virus - Biochemistry ; Chikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya virus - Molecular methods ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2014
