RESUMO
The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.
Assuntos
Epitopos/imunologia , Vacinas de DNA/imunologia , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/imunologia , Animais , DNA/genética , DNA/imunologia , Modelos Animais de Doenças , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/virologia , Humanos , Camundongos , Linfócitos T/imunologia , Linfócitos T/virologia , Proteínas não Estruturais Virais/genética , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologiaRESUMO
Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice. Leptin deficiency results in an increased frequency of Treg and Th2 cells and a prolonged graft survival. These effects of leptin deficiency indicate the importance of leptin and obesity in modulating the allograft immune responses. Our data suggest a possible explanation for the increased susceptibility of hyperleptinemic obese patients to acute and chronic graft rejection.