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1.
Sci Adv ; 5(12): eaax2388, 2019 12.
Article in English | MEDLINE | ID: mdl-31844662

ABSTRACT

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.


Subject(s)
Epitopes/immunology , Vaccines, DNA/immunology , Viral Nonstructural Proteins/immunology , Zika Virus Infection/immunology , Animals , DNA/genetics , DNA/immunology , Disease Models, Animal , Guillain-Barre Syndrome/genetics , Guillain-Barre Syndrome/immunology , Guillain-Barre Syndrome/virology , Humans , Mice , T-Lymphocytes/immunology , T-Lymphocytes/virology , Viral Nonstructural Proteins/genetics , Zika Virus/immunology , Zika Virus/pathogenicity , Zika Virus Infection/prevention & control , Zika Virus Infection/virology
2.
Am J Transplant ; 13(1): 36-44, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23016759

ABSTRACT

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.


Subject(s)
Graft Survival/physiology , Leptin/physiology , Th2 Cells/immunology , Animals , Flow Cytometry , Lymphocyte Culture Test, Mixed , Male , Mice , Mice, Inbred C57BL , Polymerase Chain Reaction , Transplantation, Homologous
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