Rocky Mountain spotted fever, the most severe and widespread rickettsiosis in the United States, and boutonneuse fever, a spotted fever group rickettsiosis with an extremely widespread geographic distribution, high prevalence of undiagnosed infections, and substantial mortality in Africa, Asia, and Europe, are neglected diseases of public health importance. The timely clinical and laboratory diagnosis of these diseases is remarkably underestimated in difficulty, and no effective prevention is available. Toward the longterm goal of elucidation of the molecular structure and function of spotted fever group rickettsiae, this proposed research is focused on the identification of protective vaccinogens of Rickettsia rickettsii, R. conorii and R. montana. Recombinant DNA production of antigens of R. conorii, R. rickettsii, and R. montana will be engineered to provide sufficient quantities of antigens for use as vaccinogens and specific probes of cellular and humoral immune responses. Antigens will be characterized by reactivity with a library of anti-spotted fever group rickettsial epitopes, which has already been partially developed, including monoclonals that protects experimental animals from virulent challenge. Because the three previous historic vaccines have failed to provide protective immunity in contrast to the solid immunity conferred by prior active infection, the immunologic basis for successful and unsuccessful vaccination will be evaluated in experimental animals. Animals vaccinated with crossprotective viable rickettsiae and purified antigens will be challenged and evaluated for the kinetics of the cellular immune response (gamma- interferon and lymphocyte proliferation) and antibody response. Moreover, the elucidation of the physiologic or pathogenic functions of rickettsial molecular components will be approached by manipulation of an assay for rickettsial attachment to the host cell. The ultimate result of these experiments should be the collection of data needed for the rational design of vaccines to prevent spotted fever group rickettsiosis, a better understanding of immunity to spotted fever group rickettsiae, and determination of the rickettsial attachment mechanism.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Medical Br Galveston
Schools of Medicine
United States
Zip Code
Bechelli, Jeremy; Smalley, Claire; Zhao, Xuemei et al. (2016) MyD88 Mediates Instructive Signaling in Dendritic Cells and Protective Inflammatory Response during Rickettsial Infection. Infect Immun 84:883-93
Walker, David H; Dumler, J Stephen (2015) The role of CD8 T lymphocytes in rickettsial infections. Semin Immunopathol 37:289-99
Villano, Jason S; Rong, Fang; Cooper, Timothy K (2014) Bacterial infections in Myd88-deficient mice. Comp Med 64:110-4
Ismail, Nahed; Walker, David H; Ghose, Purnima et al. (2012) Immune mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis. BMC Immunol 13:26
Fang, Rong; Ismail, Nahed; Walker, David H (2012) Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium. Am J Pathol 181:185-95
Xin, Lijun; Shelite, Thomas R; Gong, Bin et al. (2012) Systemic treatment with CpG-B after sublethal rickettsial infection induces mouse death through indoleamine 2,3-dioxygenase (IDO). PLoS One 7:e34062
Valbuena, Gustavo; Walker, David H (2009) Infection of the endothelium by members of the order Rickettsiales. Thromb Haemost 102:1071-9
Fang, Rong; Ismail, Nahed; Shelite, Thomas et al. (2009) CD4+ CD25+ Foxp3- T-regulatory cells produce both gamma interferon and interleukin-10 during acute severe murine spotted fever rickettsiosis. Infect Immun 77:3838-49
Jordan, Jeffrey M; Woods, Michael E; Soong, Lynn et al. (2009) Rickettsiae stimulate dendritic cells through toll-like receptor 4, leading to enhanced NK cell activation in vivo. J Infect Dis 199:236-42
Sousa, Rita de; Franca, Ana; Doria Nobrega, Sonia et al. (2008) Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients. J Infect Dis 198:576-85

Showing the most recent 10 out of 70 publications