Evaluation of Anaplasma phagocytophilum Recombinant VirB10 Protein for Protection Against Ehrlichia chaffeensis
Abstract
Rationale, Scientific Objective and Aims. Across the globe, human activities and population growth have drastically changed ecosystems and climate, expanding human-inhabited space into close proximity to wildlife habitat. Together with a warming climate in which ticks are active earlier and later each year, this has significantly intensified human exposure to tick-borne diseases carried by wild animals, the most notable being Lyme disease. However, there are many more diseases transmitted by ticks worldwide, including human anaplasmosis (HA) and human monocytic ehrlichiosis (HME), caused by the intracellular bacteria Anaplasma phagocytophilum and Ehrlichia chaffeensis, respectively. HA and HME are debilitating, flu-like illnesses that can be fatal, constituting a threat for civilians and military Service members stationed here or around the world, where they are endemic. A vaccine against HA or HME is not available. A unique trait of these disease agents is their ability to multiply in human immune cells, disabling our defenses. They achieve this by transporting molecules into the host that disarm the immune cells, using a structure that forms channels across the bacterial outer wall, called the Type 4 Secretion System (T4SS). In A. phagocytophilum and E. chaffeensis, the protein VirB10 is an essential component of the T4SS. Previous work by the Principal Investigator (PI), under the mentorship of Dr. Anthony Barbet, determined that mice vaccinated with A. phagocytophilum VirB10 (ApVirB10) developed immune responses that reduced bacterial loads in their organs (a measure of protection) after A. phagocytophilum infection, compared to infected, unvaccinated mice. VirB10 protein is highly conserved (similar) among members of this family of disease agents. Based on these preliminary results and the conserved nature of VirB10 among these organisms, the scientific objective of this proposal is to determine if mice vaccinated with ApVirB10 are also protected against HME. The proposal has three specific aims: Aim 1 - To generate VirB10 vaccines; Aim 2 - To determine if ApVirB10 vaccination induces antibodies that bind to E. chaffeensis VirB10; and Aim 3 - To determine if ApVirB10 vaccination protects mice against E. chaffeensis. This work will lay the ground for the development of a vaccine that simultaneously protects humans against HA and HME, addressing the focus area of safe and effective human vaccines against tick-borne diseases. PI’s career goals in tick-borne disease research. My career goal is to become a prominent, independent investigator who significantly contributes to human and animal health by translating basic research into therapeutics and/or vaccines for the control and prevention of tick-borne bacterial diseases. This award would be a tremendous boost to advance the PI’s career goal by providing protected time for research and funds to evaluate the cross-protective abilities of ApVirB10 against related bacteria. Moreover, critical results obtained through this work will allow her to apply for additional funding toward a larger study, focused on the development of a vaccine based on highly conserved VirB10 sequences (epitopes). Currently, the PI applies her expertise in biochemistry, molecular biology and bioinformatics to unravel the different mechanisms that these pathogens use to invade and replicate within host-cells. To achieve her goals, the PI must acquire additional skills to better understand the host responses to these pathogens and to vaccination. In addition to the proposed research, the PI and her mentors developed a comprehensive career development plan that will allow her to acquire necessary skills in important areas such as immunology, vaccinology, structural biology, and tick biology. The results obtained from the proposed work should be applicable to other intracellular bacteria. Indeed, the PI believes that this work should be applicable for a future vaccine against mul
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010184
Entities
People
- Francy L Crosby
Organizations
- United States Army
- University of Florida