[BIO Colloquium] Discovery of a novel vaccine candidate for Staphylococcus aureus infection
  • Bok Leul Lee, Ph.D. (College of Pharmacy, Pusan National University)
  • SLS Colloquia / Oct 28th 04:00 pm / AMRB 113
Abstract
 

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in clinic makes difficulty us to treat the patients who are infected with S. aureus infection. To prevent or cure MRSA infection, we need intensive studies of how hosts defend their bodies from S. aureus infection and how S. aureus strains evade the host immune responses. Many recent studies demonstrated that both serum antibody-mediated humoral immunity and T-cell-mediated cellular immunity are required to establish protective immunity against S. aureus infection. Development of these two immune responses is hypothesized to be essential for effective vaccination against S. aureus infection. However, no vaccine candidate has been identified that elicits both humoral and cellular immune responses in a murine model. Recently, we have demonstrated that S. aureus wall teichoic acid (WTA) is recognized by mannose-binding lectin (MBL) and human serum anti-WTA IgG. These studies suggest that staphylococcal WTA derivatives may induce protective immunity against S. aureus infection. To test this hypothesis, we purified several WTA derivatives from S. aureus mutant strains. Following immunization onto C57BL/6J mice with purified WTA derivatives via intradermally or peritoneally, infection with MRSA USA300 strains was performed with intravenous or peritoneal inoculation. When serum antibody titer and bacterial loads were examined, one of the WTA derivatives was found to induce production of antibody significantly, with corresponding reduction in abscess formation and decreased bacterial load in kidneys. Further investigation showed that injection of the same WTA derivative into peritoneal cavity of C57BL/6J mice resulted in significantly increased levels of γδ T cells-mediated cytokine IL-17 in peritoneal fluid within 6 hrs. But, this IL-17 production was not produced on the γδ TCR-deficient KO mice. Taken together, our results demonstrate that our novel staphylococcal WTA derivative induces both humoral immunity, as demonstrated by production of specific serum antibodies that promote opsonophagocytosis, as well as cellular immunity, as demonstrated by production of γδ T cells-mediated IL-17, which promotes neutrophil recruitment at the early stage of infection. Also, when we immunized this antigen onto intra-derma or peritoneal cavity, memory γδ T cells are generated with protective effects against MRSA USA 300 infection. Consequently, this WTA derivative is a novel vaccine candidate against staphylococcal infection.