Abstract
Despite significant economic losses resulting from infection with Anaplasma marginale, a tick-transmitted rickettsial pathogen of cattle, available vaccines provide, at best, only partial protection against clinical disease. The green-fluorescent protein expressing mutant of the A. marginale St. Maries strain is a live, marked vaccine candidate (AmStM-GFP). To test whether AmStM-GFP is safe and provides clinical protection, a group of calves was vaccinated, and clinical parameters, including percent parasitized erythrocytes (PPE), packed cell volume (PCV) and days required to reach peak bacteremia, were measured following inoculation and following tick challenge with wild type St. Maries strain (AmStM). These clinical parameters were compared to those obtained during infection with the A. marginale subsp. centrale vaccine strain (A. centrale) or wild type AmStM. AmStM-GFP resulted in similar clinical parameters to A. centrale, but had a lower maximum PPE, smaller drop in PCV and took longer to reach peak bacteremia than wild type AmStM. AmStM-GFP provided clinical protection, yielding a stable PCV and low bacteremia following challenge, whereas A. centrale only afforded partial clinical protection.
Highlights
Anaplasma marginale is a tick-transmitted rickettsial pathogen of cattle resulting in decreased production due to weight loss, abortion, lower milk yields and death in up to 36% of clinical cases [1]
To determine safety of AmStM-green fluorescent protein (GFP) as a vaccine, clinical parameters were compared between animals inoculated with AmStM-GFP versus AmStM or A. centrale
When comparing animals inoculated with cultured AmStM-GFP with those inoculated with noncultured AmStM, all measured clinical parameters were significantly different
Summary
Anaplasma marginale is a tick-transmitted rickettsial pathogen of cattle resulting in decreased production due to weight loss, abortion, lower milk yields and death in up to 36% of clinical cases [1]. Various vaccine strategies based on the immunogenic outer membrane proteins of A. marginale sensu stricto strains have been examined. Blood-derived whole outer membrane (OM) preparations and cross-linked surface proteins provide the best protection from high level bacteremia and anemia, but may not be practical for large scale production [2,3,4]. Recombinant proteins, DNA vaccines and killed preparations of A. marginale, including inactivated cell-culture derived organisms, have failed to recapitulate the protection seen with OM based vaccines [5,6,7,8,9,10]. Vaccine induced protection is complex and requires more than antibodies to immunodominant proteins, as studies have repeatedly demonstrated specific seroconversion in the face of failure of clinical protection [5, 10, 11]. Advantages offered by a live vaccine include a full complement of surface antigens in their native conformations, and presentation of new surface protein variants over time
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