Revealing the attenuating mutations of F. tularensis                              LVS

Recombinant Antigen-based Assays for Flavivirus                              Serodiagnosis and                              Surveillance

Identification and Inhibition of Cytokines Induced                              During OHFV Infection

Cell Wall Proteins in Bacillus anthracis as
                      Vaccines

Rational Design and Optimization of New Live-                              attenuated Vaccines for                              Alphaviral Enciphalitides

Nodavirus-based RNA Replicon Vaccines for                              Tick-borne Encephalitis                               Virus

Antiviral Agents as Therapy for SARS

Typhus Group Rickettsial Antigens Recognized by                              CD8+ T Lymphocytes

Cell Wall Proteins in Bacillus anthracis as Vaccines

Institution: Texas A&M University System Health Science Center at Houston, Houston, TX

Principal Investigator: Yi Xu, Ph.D.

Mentors:
a) Theresa M. Koehler, Ph.D. - The University of Texas Health Science Center at Houston, Houston, TX
b) C. Rick Lyons, M.D., Ph.D. - University of New Mexico Health Sciences Center, Albuquerque, NM

Expected Product: Subunit vaccine candidates for anthrax.

Description: Anthrax is an old disease with re-born relevance to both scientists and the public. The current human anthrax vaccine, Anthrax Vaccine Absorbed (AVA), consists of protective antigen (PA) as the principal protective immunogen and other uncharacterized minor components. It requires a lengthy administration procedure with annual boosters and may have undesirable side effects. Several studies indicate that immunogens in addition to PA are required for full and long-lasting immunity to anthrax. Consequently, it is important to develop a vaccine that has defined components, affords long-term protection and has reduced side effects. Gram-positive pathogenic bacteria possess cell wall anchored proteins (CWAPs) that are critical for virulence and are excellent vaccine candidates. By analogy, the CWAPs of B. anthracis are likely to show equal relevance and utility. Analysis of the B. anthracis genome revealed nine previously uncharacterized CWAPs. Preliminary studies indicated a recombinant fragment of one of these recognized specific macrophage targets. Two additional CWAPs were found to bind collagen, which is a major component of the skin where cutaneous anthrax develops. These three proteins were shown to be expressed in B. anthracis by western blot analysis. Together these findings support the hypothesis that CWAPs of B. anthracis are significant in its pathogenesis and are potential vaccine candidates. The aims of this proposal are: 1) to determine the protective efficacy of the nine CWAPs in a murine pulmonary anthrax model against challenge from a virulent B. anthracis and 2) to determine if the CWAPs contribute to the virulence of B. anthracis. These studies will be performed in collaboration with Dr. Theresa Koehler at University of Texas Medical School, and Dr. Rick Lyons at the University of New Mexico. I hypothesize that results from these studies will lead to the development of new human anthrax vaccines and provide an initial mechanistic understanding of the roles of these proteins in B. anthracis pathogenesis. This will set the foundation for future research with the long term goal of developing improved human vaccines through a better understanding of the molecular interactions of B. anthracis and its host.