Through a Career Development Award funded by the United States Department of Defense, Francy L. Crosby, Ph.D., a research scientist at UF, will evaluate an alternative vaccine strategy that could produce simultaneous protection against two closely related tick-borne bacteria species.
The two-year grant is for $381,250. Crosby’s collaborators include Anthony Barbet, Ph.D., a professor emeritus at UF, David Pascual, Ph.D., a professor of infectious diseases and immunology at UF, and Ulrike Munderloh, D.V.M, Ph.D., of the University of Minnesota.
“In North America and other temperate regions, emerging bacterial tick-borne diseases such as human anaplasmosis, or HA, and human monocytic ehrlichiosis, or HME, caused by the Rickettsiales Anaplasma phagocytophilum and Ehrlichia chaffeensis, respectively, are among the top five most diagnosed tick-borne zoonotic infectious diseases,” Crosby said. “These diseases are debilitating, flu-like illnesses that are potentially fatal and rapidly expanding here and worldwide.”
Crosby added that these two pathogens also infect domestic animals and wildlife; therefore, companion animals such as dogs and cats also constitute a risk group for these agents, as they frequently go outdoors becoming exposed to vector arthropods.
“Often, complications with these diseases will require hospitalization — between 40-70% — and illness may progress to a severe multisystem disease that resembles sepsis or toxic shock like-syndrome with a case fatality rate of 1-3%,” she said. “Similarly, immunocompromised persons are at higher risk of acquiring HA or HME, and to experience severe illness. Unfortunately, a vaccine against HA or HME is not available.”
A unique trait of these disease agents is their ability to multiply in immune cells, disabling our defenses, Crosby said: “They achieve this by transporting molecules into the host cells using a structure that forms channels across the bacterial envelope. This structure is known as the Type 4 Secretion System or T4SS.”
In A. phagocytophilum and E. chaffeensis, the protein VirB10 is an essential component of the T4SS. Previous work by Crosby, in collaboration with Barbet, determined that mice vaccinated with VirB10 developed immune responses that reduced bacterial loads after A. phagocytophilum infection.
“One good thing is that VirB10 is highly similar between A. phagocytophilum and E. chaffeensis. Therefore, this project will test if mice vaccinated with VirB10 derived from A. phagocytophilum will elicit immune responses that will protect these animals against E. chaffeensis infection,” Crosby said. “If successful, we will provide, for the first time, proof of principle that protection against both diseases is achievable by cross protection with a single vaccine.”
This work will be applicable to other pathogenic bacteria carrying VirB10. Crosby said the project will also point toward a new direction for the discovery of additional protective antigens that are highly similar among closely related tick-borne Rickettsiales and will benefit from the ever-increasing amounts of genomics, transcriptomics and proteomics data available for several of these pathogens.