Desenvolvimento de vacinas recombinantes contra malária humana e teste in vivo em modelo murino

• Ano de defesa: 2009
• Autor(a) principal: Leoneide Erica Maduro Boillet
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: malária; MSP-119; Adenovírus humano sorotipo 5; vacinas recombinantes; AMA-1; Microbiologia; Adenovirus; Antígeno de membrana apical (AMA-1); Malária
• Link de acesso: http://hdl.handle.net/1843/BUOS-8MYGD7

Vaccines that provide protection against malaria are urgently needed fordisease control. Several studies have demonstrated that Apical membrane antigen-1 (AMA-1) and 19KDa fragment of merozoit surface protein (MSP-119) are the main vaccine candidates against blood stages of malaria due to their capacity to induce protection in humans and animals. In this study, we investigated the effect of P. vivax vaccine candidates genetically modified PvAMA-1 and PvMSP-1 in different combinations of prime-boost immunization protocols. With this aim we constructed recombinant adenoviruses expressing PvAMA-1 and PvMSP-1 to active and modulate an effective type of T-cell response. Equivalent recombinant polypeptides purified from E.coli-expressing bacteria were used to induce humoral response. After the characterization of vaccine antigens, BALB/c mice were immunized with virus and proteins formulated in Montanide ISA 720 adjuvant. The animals vaccinated with the following immunization protocols Ad/Ad, Ad/prot, prot/prot and prot/Ad generated specific anti-PvAMA-1 and anti-PvMSP-119 IgG antibodies. However, the prime-boost protocols prot/prot and prot/Ad efficiently enhanced antibodies response, showing high antibody titers to AMA-1 and MSP-119. PvAMA-1 was able to induce specific antigen-cellular proliferation and the protocols Ad/Ad and prot/prot were able to induce highest levels of cell proliferation. PvMSP-119 was able of elicited cell responses predominantly a Th1-biased, inducing higher levels of IFN-g, IL-2 e TNF-a. Furthermore, it was able to induce the production of IL-10 but not triggered the production of IL-4. In such way, we conclude that immunization with the prime-boost protocols prot/prot and prot/Ad induced efficient humoral and cellular immune response. In the other hand, Ad/Ad elicited efficient cellular immune response. These results are encouraging for preclinical studies in monkeys Aotus spp using the following three protocols prot/prot, prot/Ad and Ad/Ad