Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis

Authors: ALZAN, HEBA - Washington State University; BASTOS, REGINALDO - Washington State University; Ueti, Massaro; LAUGHERY, JACOB - Washington State University; RATHINASAMY, VIGNESH - James Cook University; COOKE, BRIAN - James Cook University; Suarez, Carlos

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2021
Publication Date: 4/20/2021
Citation: Alzan, H.F., Bastos, R.G., Ueti, M.W., Laughery, J.M., Rathinasamy, V.A., Cooke, B.M., Suarez, C.E. 2021. Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis. Parasites & Vectors. 14. Article 210. https://doi.org/10.1186/s13071-021-04712-7.
DOI: https://doi.org/10.1186/s13071-021-04712-7

Interpretive Summary: Babesia bovis reproduce sexually in the midgut of its tick vector Rhipicephalus microplus, a process involving expression of the 6cys A and B proteins. In this study we evaluated, for the first time, the potential of eukaryotic, recombinant 6cys A and 6cys B (r6cysA-B) proteins as candidates for a transmission blocking vaccine (TBV) against B. bovis in a cattle vaccine trial. Vaccinated cattle developed antibodies reacting with r6cys A and B proteins, but failed to recognize native versions of the proteins and were unable to block sexual reproduction of the parasite in ticks. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of both proteins recognized recombinant and native forms of 6cys proteins in immunoblots, and were able to neutralize in vitro development of sexual forms of the parasite. Analysis of immune responses in vaccinated animals suggested that vaccine failure may be due to the lack of antibodies that react with epitopes located in key functional domains of the 6cys A and 6cys B proteins. These data, combined with previous work performed on Plasmodium 6cys proteins, indicate that effective 6cys protein based TBV against B. bovis will require identifying and targeting selected regions of the proteins containing transmission reduction epitopes.

Technical Abstract: Babesia bovis reproduce sexually in the midgut of its tick vector Rhipicephalus microplus, a process involving expression of the 6cys A and B proteins. We evaluated, for the first time, the potential of eukaryotic, recombinant 6cys A and 6cys B (r6cysA-B) proteins as candidates for a transmission blocking vaccine (TBV) against B. bovis in a cattle vaccine trial. Vaccinated cattle developed antibodies reacting with r6cys A and B proteins, but failed to recognize native versions of the proteins and were unable to block sexual reproduction of the parasite in ticks. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of both proteins recognized recombinant and native forms of 6cys proteins in immunoblots, and were able to neutralize in vitro development of sexual forms of the parasite. Analysis of immune reponses in vaccinated animals suggested that vaccine failure may be due to the lack of antibodies that react with epitopes located in key functional domains of the 6cys A and 6cys B proteins. These data, combined with previous work performed on Plasmodium 6cys proteins, indicate that effective 6cys protein based TBV against B. bovis will require identifying and targeting selected regions of the proteins containing transmission reduction epitopes.