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

BACKGROUND: Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicit...

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Autores principales: Alzan, Heba F., Bastos, Reginaldo G., Ueti, Massaro W., Laughery, Jacob M., Rathinasamy, Vignesh A., Cooke, Brian M., Suarez, Carlos E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056569/
https://www.ncbi.nlm.nih.gov/pubmed/33879245
http://dx.doi.org/10.1186/s13071-021-04712-7
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author Alzan, Heba F.
Bastos, Reginaldo G.
Ueti, Massaro W.
Laughery, Jacob M.
Rathinasamy, Vignesh A.
Cooke, Brian M.
Suarez, Carlos E.
author_facet Alzan, Heba F.
Bastos, Reginaldo G.
Ueti, Massaro W.
Laughery, Jacob M.
Rathinasamy, Vignesh A.
Cooke, Brian M.
Suarez, Carlos E.
author_sort Alzan, Heba F.
collection PubMed
description BACKGROUND: Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicity of the 6cys proteins in the related Plasmodium parasites required the identification of transmission blocking domains in these molecules for vaccine design. Hereby, the immunogenic efficacy of recombinant (r) B. bovis 6cys A and B proteins as a TBV formulation was studied. METHODS: The immunogenicity of r6cys A and 6cys B proteins expressed in a eukaryotic system was evaluated in a cattle immunization trial (3 immunized and 3 control calves). A B. bovis sexual stage induction in vitro inhibition assay to assess the ability of antibodies to block the production of sexual forms by the parasite was developed. RESULTS: Immunized cattle generated antibodies against r6cys A and r6cys B that were unable to block sexual reproduction of the parasite in ticks. Additionally, these antibodies also failed in recognizing native 6cys A and 6cys B and peptides representing 6cys A and 6cys B functional domains and in inhibiting the development of sexual forms in an in vitro induction system. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of 6cys A and 6cys B recognized recombinant and native forms of both 6cys proteins as well as peptides representing 6cys A and 6cys B functional domains and were able to neutralize development of sexual forms of the parasite in vitro. CONCLUSIONS: These data, combined with similar work performed on Plasmodium 6cys proteins, indicate that an effective 6cys protein-based TBV against B. bovis will require identifying and targeting selected regions of proteins containing epitopes able to reduce transmission. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-021-04712-7.
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spelling pubmed-80565692021-04-20 Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis Alzan, Heba F. Bastos, Reginaldo G. Ueti, Massaro W. Laughery, Jacob M. Rathinasamy, Vignesh A. Cooke, Brian M. Suarez, Carlos E. Parasit Vectors Research BACKGROUND: Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicity of the 6cys proteins in the related Plasmodium parasites required the identification of transmission blocking domains in these molecules for vaccine design. Hereby, the immunogenic efficacy of recombinant (r) B. bovis 6cys A and B proteins as a TBV formulation was studied. METHODS: The immunogenicity of r6cys A and 6cys B proteins expressed in a eukaryotic system was evaluated in a cattle immunization trial (3 immunized and 3 control calves). A B. bovis sexual stage induction in vitro inhibition assay to assess the ability of antibodies to block the production of sexual forms by the parasite was developed. RESULTS: Immunized cattle generated antibodies against r6cys A and r6cys B that were unable to block sexual reproduction of the parasite in ticks. Additionally, these antibodies also failed in recognizing native 6cys A and 6cys B and peptides representing 6cys A and 6cys B functional domains and in inhibiting the development of sexual forms in an in vitro induction system. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of 6cys A and 6cys B recognized recombinant and native forms of both 6cys proteins as well as peptides representing 6cys A and 6cys B functional domains and were able to neutralize development of sexual forms of the parasite in vitro. CONCLUSIONS: These data, combined with similar work performed on Plasmodium 6cys proteins, indicate that an effective 6cys protein-based TBV against B. bovis will require identifying and targeting selected regions of proteins containing epitopes able to reduce transmission. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-021-04712-7. BioMed Central 2021-04-20 /pmc/articles/PMC8056569/ /pubmed/33879245 http://dx.doi.org/10.1186/s13071-021-04712-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Alzan, Heba F.
Bastos, Reginaldo G.
Ueti, Massaro W.
Laughery, Jacob M.
Rathinasamy, Vignesh A.
Cooke, Brian M.
Suarez, Carlos E.
Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title_full Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title_fullStr Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title_full_unstemmed Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title_short Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis
title_sort assessment of babesia bovis 6cys a and 6cys b as components of transmission blocking vaccines for babesiosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056569/
https://www.ncbi.nlm.nih.gov/pubmed/33879245
http://dx.doi.org/10.1186/s13071-021-04712-7
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