Generation of babesial surface protein diversity
Principal Investigator: Shawn J Berens
Abstract: Research Proposal: Introduction of antigenically diverse populations of hemoparasites in previously infected or immunized individuals permits clinical disease through evasion of host immunity. Limited information is currently available on the contribution of the arthropod phase of the lifecycle, especially in ticks, to the antigenic diversity of hemoparasites. Antigenic diversity created during this phase may be largely responsible for the variability observed in many surface proteins. The research proposed herein aims to determine whether the vector influences antigenic diversification, by what mechanisms these changes occur, and how this diversity affects immunologically relevant epitopes. The hemoparasite model we will use for this research is infection of cattle with Babesia bovis. For B. bovis, merozoite surface antigen2 (msa-2) genes from vaccine breakthrough isolates examined are significantly different from the msa-2 genes of the vaccine strains used to immunize these animals. This finding strongly suggests that changes in these genes may contribute to immune system evasion. Two hypotheses will be tested. The first is that the generation of nucleotide variation in the msa-2a and -2b genes of B. bovis occurs within the tick vector. The second is that msa-2a and -2b genes among distinct strains of B. bovis encode strain-specific inhibition-sensitive B-cell epitopes. Understanding how, when, and where antigenic diversity is generated will address a major gap in our knowledge regarding protective immunity and breakthroughs in vaccinated or previously infected individuals. The Candidate: The candidate is a veterinarian completing a residency in comparative anatomic pathology and a Ph.D. degree. The candidate has fulfilled most of the requirements of his pathology training along with all didactic course work and his candidacy exam, and is actively pursuing the research portion of his training. This research proposal constitutes his plan to investigate immunologic mechanisms of hemoparasitic infection. Environment: The Department of Veterinary Microbiology and Pathology at Washington State University provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education, residency programs, and extensive collaboration both within and outside the university. The sponsors collaborate closely in research and have successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.
Funding Period: 2004-07-01 - 2008-03-31
more information: NIH RePORT
- Merozoite surface antigen 2 proteins of Babesia bovis vaccine breakthrough isolates contain a unique hypervariable region composed of degenerate repeatsShawn J Berens
Program in Vector Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164 7040, USA
Infect Immun 73:7180-9. 2005..Variation in length and content of the HVR is primarily attributable to differences in the order and number of degenerate nucleotide repeats encoding three motifs of unknown function...
- Coinfection with antigenically and genetically distinct virulent strains of Babesia bovis is maintained through all phases of the parasite life cycleShawn J Berens
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164 7040, USA
Infect Immun 75:5769-76. 2007..While coinfection of the tick vector provides the context in which allelic antigenic diversity can be generated, recombination of VMSA genes could not be confirmed, suggesting that VMSA allelic changes are slow to accumulate...