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Infection and Immunity, September 2005, p. 5388-5394, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5388-5394.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sequence Variation and Immunologic Cross-Reactivity among Babesia bovis Merozoite Surface Antigen 1 Proteins from Vaccine Strains and Vaccine Breakthrough Isolates

Tanya LeRoith,1* Kelly A. Brayton,1 John B. Molloy,2 Russell E. Bock,3 Stephen A. Hines,1 Ala E. Lew,2 and Terry F. McElwain1

Program in Vector-Borne Diseases, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040,1 Emerging Technologies/Delivery, Queensland Department of Primary Industries and Fisheries, Moorooka 4105, Queensland, Australia,2 Tick Fever Centre, Biosecurity, Queensland Department of Primary Industries and Fisheries, Wacol, Queensland, Australia3

Received 21 January 2005/ Returned for modification 8 March 2005/ Accepted 6 May 2005

The Babesia bovis merozoite surface antigen 1 (MSA-1) is an immunodominant membrane glycoprotein that is the target of invasion-blocking antibodies. While antigenic variation has been demonstrated in MSA-1 among strains from distinct geographical areas, the extent of sequence variation within a region where it is endemic and the effect of variation on immunologic cross-reactivity have not been assessed. In this study, sequencing of MSA-1 from two Australian B. bovis vaccine strains and 14 breakthrough isolates from vaccinated animals demonstrated low sequence identity in the extracellular region of the molecule, ranging from 19.8 to 46.7% between the T vaccine strain and eight T vaccine breakthrough isolates, and from 18.7 to 99% between the K vaccine strain and six K vaccine breakthrough isolates. Although MSA-1 amino acid sequence varied substantially among strains, overall predicted regions of hydrophilicity and hydrophobicity in the extracellular domain were conserved in all strains examined, suggesting a conserved functional role for MSA-1 despite sequence polymorphism. Importantly, the antigenic variation created by sequence differences resulted in a lack of immunologic cross-reactivity among outbreak strains using sera from animals infected with the B. bovis vaccine strains. Additionally, sera from cattle hyperinfected with the Mexico strain of B. bovis and shown to be clinically immune did not cross-react with MSA-1 from any other isolate tested. The results indicate that isolates of B. bovis capable of evading vaccine-induced immunity contain an msa-1 gene that is significantly different from the msa-1 of the vaccine strain, and that the difference can result in a complete lack of cross-reactivity between MSA-1 from vaccine and breakthrough strains in immunized animals.


* Corresponding author. Mailing address: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040. Phone: (509) 335-6339. Fax: (509) 335-8529. E-mail: tleroith{at}vetmed.wsu.edu.

Editor: W. A. Petri, Jr.


Infection and Immunity, September 2005, p. 5388-5394, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5388-5394.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Berens, S. J., Brayton, K. A., McElwain, T. F. (2007). Coinfection with Antigenically and Genetically Distinct Virulent Strains of Babesia bovis Is Maintained through All Phases of the Parasite Life Cycle. Infect. Immun. 75: 5769-5776 [Abstract] [Full Text]  
  • LeRoith, T., Berens, S. J., Brayton, K. A., Hines, S. A., Brown, W. C., Norimine, J., McElwain, T. F. (2006). The Babesia bovis Merozoite Surface Antigen 1 Hypervariable Region Induces Surface-Reactive Antibodies That Block Merozoite Invasion. Infect. Immun. 74: 3663-3667 [Abstract] [Full Text]  
  • Berens, S. J., Brayton, K. A., Molloy, J. B., Bock, R. E., Lew, A. E., McElwain, T. F. (2005). Merozoite Surface Antigen 2 Proteins of Babesia bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats. Infect. Immun. 73: 7180-7189 [Abstract] [Full Text]