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Identification of Anaplasma marginale outer membrane protein antigens conserved between A. marginale sensu stricto
Joseph T Agnes1, Kelly A Brayton, Megan LaFollett
1Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA.
Abstract:
Live vaccination with Anaplasma marginale subsp. centrale (synonym for Anaplasma centrale) induces protection against severe disease upon challenge with A. marginale sensu stricto strains. Despite over a century of field use, the targets of protective immunity remained unknown. Using a broad proteomic approach, we identified the proteins in a challenge sensu stricto strain that were bound by the relevant antibody isotype induced by live vaccination with Anaplasma marginale subsp. centrale. A core of 15 proteins was identified in vaccinated animals across multiple major histocompatibility complex (MHC) haplotypes. This core separated into two structural/functional classes: "housekeeping" proteins involved in replication and metabolism and outer membrane proteins (OMPs). Orthologous proteins of both classes were identified within the vaccine strain and among sensu stricto strains. In contrast to the broad conservation among strains in the sequences of the housekeeping proteins, there was significantly greater divergence in the OMPs and greater divergence in both OMP sequences and the encoding locus structure between the vaccine strain and the sensu stricto strains than among the sensu stricto strains. The OMPs bound by live vaccine-induced antibody overlapped with OMPs that were immunogenic in animals vaccinated with inactivated vaccines and subsequently protected against bacteremia and disease. The identification of this core set of OMPs is consistent with the hypothesis that "subdominant" immunogens are required for vaccine-induced protection against A. marginale and provides clear direction for development of a safer, more effective vaccine.
Insights
Live vaccination with Anaplasma marginale subsp. centrale protects against severe disease. Researchers identified 15 key proteins, including outer membrane proteins (OMPs), targeted by protective antibodies, guiding future vaccine development.
Area of Science:
- Veterinary Immunology
- Bacteriology
- Vaccinology
Background:
- Live vaccination with Anaplasma marginale subsp. centrale provides protection against A. marginale challenge.
- The specific targets of this protective immunity have remained unidentified for over a century.
Purpose of the Study:
- To identify the proteins targeted by antibodies induced by live Anaplasma marginale subsp. centrale vaccination.
- To understand the antigenic targets crucial for protective immunity against Anaplasma marginale.
Main Methods:
- Utilized a proteomic approach to identify proteins from A. marginale sensu stricto bound by antibodies from live vaccine recipients.
- Analyzed protein sequence conservation and locus structure between vaccine and challenge strains.
Main Results:
- Identified a core set of 15 proteins, including housekeeping and outer membrane proteins (OMPs), recognized by vaccine-induced antibodies.
- Found significant sequence divergence in OMPs between the vaccine strain and challenge strains.
- OMPs identified were also immunogenic in animals receiving inactivated vaccines and conferred protection.
Conclusions:
- The study identifies a core set of outer membrane proteins (OMPs) as key targets for protective immunity against Anaplasma marginale.
- These findings support the hypothesis that subdominant immunogens are critical for effective vaccines.
- Provides a foundation for developing safer and more effective Anaplasma marginale vaccines.
