RESUMO
This study explores the utility of recombinant adeno-associated virus (rAAV) as a genetic vaccine delivery system using muscle as a target tissue. A single injection of rAAV encoding the malarial antigens MSP4 (Plasmodium falciparum) or MSP4/5 (Plasmodium yoelii) stimulated long-term antigen-specific antibody responses. Anti-MSP4/5 immunity stimulated by AAV was not protective against P. yoelii infection and efforts taken to augment antibody responses against MSP4/5, either by priming with plasmid DNA or AAV and boosting with rAAV were unsuccessful. Alternative strategies such as inclusion of genetic adjuvants into the AAV vector will be necessary to stimulate an adequate level of anti-malarial protective immunity in this model.
Assuntos
Antígenos de Protozoários/imunologia , Dependovirus/genética , Vacinas Antimaláricas/administração & dosagem , Malária/imunologia , Proteínas de Membrana/imunologia , Plasmodium falciparum/imunologia , Plasmodium yoelii/imunologia , Proteínas de Protozoários/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Formação de Anticorpos/imunologia , Antígenos de Protozoários/genética , Dependovirus/imunologia , Epitopos , Feminino , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Células HeLa , Humanos , Injeções Intramusculares , Malária/parasitologia , Malária/prevenção & controle , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium falciparum/parasitologia , Plasmodium yoelii/parasitologia , Proteínas de Protozoários/genéticaRESUMO
The youngest (rings and young trophozoites) erythrocytic stages of Plasmodium yoelii nigeriensis and P. yoelii killicki, two rodent malaria subspecies developing very asynchronously in the blood, were separated from the other stages using a discontinuous Percoll-glucose gradient. They were inoculated into mice and the subsequent infection remained synchronous for two generations. The duration of the asexual cycle was found to be 18 h.