Potencialização do efeito protetor e da memória imunológica pela utilização do adjuvante CAF01 associado a antígenos totais de Leishmania amazonensis (LaAg) pela via intranasal contra a Leishmaniose visceral murina

• Ano de defesa: 2014
• Autor(a) principal: Leal, Janine Miranda
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Doenças Infecciosas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Doenças Infecciosas
• Palavras-chave em Português: Memória imunológica; Administração intranasal; Leishmania chagasi; Imunização intranasal; Resposta imune; Leishmaniose visceral; Memória - Imunologia; Doenças Infecciosas e Parasitárias; 61
• Link de acesso: http://repositorio.ufes.br/handle/10/1595

The dimethyldioctadecylammonium (DDA) is a quaternary ammonium compound formed by a synthetic amphiphilic lipid comprising a hydrophilic positively charged dimethylammonium head–group attached to two hydrophobic 18-carbon alkyl chains (tail), that has previously been reported for eliciting cell-mediated and humoral responses against pathogens like Mycobacterium tuberculosis and Chlamydia trachomatis. In the present study, we investigated the ability of CAF adjuvant associated with surface antigens of Leishmania amazonensis (LaAg) to induce immunogenic and protective responses in challenge against L. chagasi. So, BALB/c mice were vaccinated by intranasal route with 2 doses of LaAg (25 mg) or LaAg associated with CAF (150 mg) intercalated by 15 days. The measurement of transaminases and creatinine in the animals sera demonstrated the biocompatibility and safety of the LaAg/CAF combination. Besides, IFN-γ and NO produced by splenocytes after LaAg in vitro recall was significantly increased, beyond significantly lymphoproliferative responses and increase of memory cells (TCD4+ CD44+ CD62L+) percentage. Increased IgG and specific subclasses (IgG1 and IgG2a) in sera levels were also observed in mice vaccinated with LaAg associated with CAF when compared to controls. Similarly, animals vaccinated with this formulation and challenged with L. chagasi 15 days after the booster with L. chagasi showed a significant decrease in parasite load in the spleen and liver, associated with increased production of IFN-γ and increased lymphoproliferative responses. Together, our results demonstrate for the first time the feasibility of intranasal vaccine with LaAg/CAF as a effective mechanism for the vaccination against visceral leishmaniasis.