The Immunization-induced Antibody Response to the Anaplasma Marginale Major Surface Protein 2 and Its Association with Protective Immunity

Many vector-borne pathogens evade clearance via rapid variation in their immunogenic surface expressed proteins. This is exemplified by Anaplasma marginale, a tick-borne bacterial pathogen that generates major surface protein 2 (Msp2) variants to provide for immune escape and allow long-term pathogen persistence. In contrast to persistence following infection, immunization with a surface protein complex, which includes Msp2, induces a response that prevents infection upon challenge. We hypothesized that the immune response induced by immunization altered the anti-Msp2 antibody repertoire as compared to that induced during infection, shifting the immune response toward conserved and thus broadly protective epitopes. The antibody response to the conserved (CR) and hypervariable (HVR) regions encoded by the full set of msp2 variant alleles was determined for immunized animals prior to challenge and non-immunized, infected animals. While both groups of animals had a similar antibody repertoire in terms of breath and magnitude, the titers to the Msp2 CR were strongly correlated (p<0.005) with control of bacteremia only in the infected animals. Among the immunized animals, there was no correlation between the breadth or magnitude of the anti-Msp2 antibody response and either complete protection from infection or control of bacteremia. This is consistent with separate immunologic mechanisms being responsible for control of bacteremia in infected animals as compared to immunized animals and suggests that conserved outer membrane proteins other than Msp2 are responsible for the complete clearance observed following challenge of vaccinees.