Autor(es)Hallengärd David, Kakoulidou Maria, Lulla Aleksei, Kümmerer Beate M, Johansson Daniel X, Mutso Margit, Lulla Valeria, Fazakerley John K, Roques Pierre, Le Grand Roger, Merits Andres, Liljeström Peter

ResumoChikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that has caused severe epidemics in Africa - Asia - occasionally in Europe. As of today, there is no licensed vaccine available to prevent CHIKV infection. Here we describe the development - evaluation of novel CHIKV vaccine c-idates that were attenuated by deleting a large part of the gene encoding nsP3 or the entire gene encoding 6K - were administered as viral particles or infectious genomes launched by DNA. The resulting attenuated mutants were genetically stable - elicited high magnitudes of binding - neutralizing antibodies as well as strong T cell responses after a single immunization in C57BL/6 mice. Subsequent challenge with a high dose of CHIKV demonstrated that the induced antibody responses protected the animals from viremia - joint swelling. The protective antibody response was long-lived, - a second homologous immunization further enhanced immune responses. In summary, this report demonstrates a straightforward means of constructing stable - efficient attenuated CHIKV vaccine c-idates that can be administered either as viral particles or as infectious genomes launched by DNA. Similar to other infectious diseases, the best means of preventing CHIKV infection would be by vaccination using an attenuated vaccine platform which preferably raises protective immunity after a single immunization. However, the attenuated CHIKV vaccine c-idates developed to date rely on a small number of attenuating point mutations - are at risk of being unstable or even sensitive to reversion. We report here the construction - preclinical evaluation of novel CHIKV vaccine c-idates that have been attenuated by introducing large deletions. The resulting mutants proved to be genetically stable, attenuated, highly immunogenic, - able to confer durable immunity after a single immunization. Moreover, these mutants can be administered either as viral particles or as DNA-launched infectious genomes, enabling evaluation of the most feasible vaccine modality for a certain setting. These CHIKV mutants could represent stable - efficient vaccine c-idates against CHIKV.

ImprentaJournal of Virology, v. 88, n. 5, p. 2858-2866, 2014

DescritoresChikungunya virus - Cell ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Immune response ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology ; Chikungunya virus - Public health

Data de Publicação:2014