Yersinia pestis is the causative agent of pneumonic plague. Development of a vaccine that protects against inhalation infection and ensuing pneumonic plague is of the utmost importance. Prior vaccination strategies, focusing on the development of a protective humoral response, have generated effective protection against the bubonic form of infection, however these strategies have provided incomplete protection against pneumonic infection. Recent investigations have revealed that F1-V protein subunit vaccination affords protection early during the course of a pneumonic infection in non-human primates, however late breakthrough of organism is found even in the presence of high Yersinia-specific antibody titers. We hypothesize that a vaccine that generates cell mediated immunity, particularly type 1 cytokine-producing (TH1) V protein-specific CD4+ T cells, in addition to stimulating humoral immunity, will protect against a pneumonic infection with Y. pestis.
Aim 1 will generate class II MHC multimers for tracking V specific CD4+ T cells. It will also optimize vaccination regimens for production of memory V specific CD4+ T cells and determine if they are protective against lethal aerosol challenge.
Aim 2 studies the protective immune response produced by a live, attenuated vaccine strain that is known to generate protection against pneumonic plague.
| Parent, Michelle A; Wilhelm, Lindsey B; Kummer, Lawrence W et al. (2006) Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection. Infect Immun 74:3381-6 |
