Babesia bovis AMA-1, MSA-2c and RAP-1 contain conserved B and T-cell epitopes, which generate neutralizing antibodies and a long-lasting Th1 immune response in vaccinated cattle

Hidalgo-Ruiz, Mario; Mejia-López, Susana; Pérez-Serrano, Rosa M.; Larrea, Guadalupe Zaldívar-Lelo de; Ganzinelli, Sabrina; Florín-Christensen, Mónica; Suárez, Carlos E.; Hernández-Ortíz, Rubén; Mercado-Uriostegui, Miguel Angel; Rodríguez-Torres, Angelina; Carvajal-Gamez, Bertha Isabel; Camacho-Nuez, Minerva; Wilkowsky, Silvina Elizabeth; Mosqueda, Juan

doi:10.1016/j.vaccine.2022.01.023

Cited by 15 publications

(18 citation statements)

References 37 publications

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“…However, the fact that the immune system recognizes conserved B-epitopes and generates antibodies against them in most cattle in the endemic areas tested supports the hypothesis that these conserved B-cell epitopes are immunogenic. These results are similar to those observed in other studies analyzing conserved B-cell epitope immunogenicity in other membrane-bound or organelle-secreted antigens in both B. bigemina and B. bovis [ 14 , 27 , 28 , 35 , 36 , 37 ]. This similarity suggests that those antigens are exposed to the immune system.…”

Section: Discussionsupporting

confidence: 91%

“…However, this observation is not always true. When we mixed serum from each peptide and tested them together, the reduction in parasite counts was greater than that observed for individual peptides for different antigens [ 35 , 37 ]. Therefore, it is important to test antisera against each individual peptide and to determine its neutralizing ability.…”

Section: Discussionmentioning

confidence: 99%

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Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata

et al. 2023

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Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus Babesia. Its main causative agents in the Americas are Babesia bigemina and Babesia bovis, while Babesia ovata affects cattle in Asia. All Babesia species secrete proteins stored in organelles of the apical complex, which are involved in all steps of the invasion process of vertebrate host cells. Unlike other apicomplexans, which have dense granules, babesia parasites instead have large, round intracellular organelles called spherical bodies. Evidence suggests that proteins from these organelles are released during the process of invading red blood cells, where spherical body proteins (SBPs) play an important role in cytoskeleton reorganization. In this study, we characterized the gene that encodes SBP4 in B. bigemina. This gene is transcribed and expressed in the erythrocytic stages of B. bigemina. The sbp4 gene consists of 834 nucleotides without introns that encode a protein of 277 amino acids. In silico analysis predicted a signal peptide that is cleaved at residue 20, producing a 28.88-kDa protein. The presence of a signal peptide and the absence of transmembrane domains suggest that this protein is secreted. Importantly, when cattle were immunized with recombinant B. bigemina SBP4, antibodies identified B. bigemina and B. ovata merozoites according to confocal microscopy observations and were able to neutralize parasite multiplication in vitro for both species. Four peptides with predicted B-cell epitopes were identified to be conserved in 17 different isolates from six countries. Compared with the pre-immunization sera, antibodies against these conserved peptides reduced parasite invasion in vitro by 57%, 44%, 42%, and 38% for peptides 1, 2, 3, and 4, respectively (p < 0.05). Moreover, sera from cattle infected with B. bigemina cattle contained antibodies that recognized the individual peptides. All these results support the concept of spb4 as a new gene in B. bigemina that should be considered a candidate for a vaccine to control bovine babesiosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata

et al. 2023

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“…Although many epitopes of sbp-2 and rap-1a amino acid sequences were conserved as functional peptides, they are not located within the signal peptide. In addition, the sbp-2 and rap-1 proteins were identified as the conserved peptide containing B-cell epitopes in B. bovis that involved Th 1 immune response in an in vivo study ( Gallego-Lopez et al., 2019 ; Hidalgo-Ruiz et al., 2022 ). However, further research into the functional properties of the rap-1a protein in B. bigemina was required.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization and genetic diversity of Babesia bovis and Babesia bigemina of cattle in Thailand

Srionrod

Nooroong

Poolsawat

et al. 2022

Front. Cell. Infect. Microbiol.

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Babesia bovis and B. bigemina are the most common tick-borne parasites that cause bovine babesiosis which effects livestock production, leading to economic losses in tropical and subtropical areas of the world. The aims of this study were to determine the molecular detection, genetic diversity and antigenicity prediction of B. bovis based on spherical body protein 2 (sbp-2) gene and B. bigemina based on rhoptry-associated protein 1a (rap-1a) gene in cattle in Thailand. By PCR assay, the molecular detection of B. bovis and B. bigemina infection revealed levels of 2.58% (4/155) and 5.80% (9/155), respectively. The phylograms showed that B. bovis sbp-2 and B. bigemina rap-1a sequences displayed 5 and 3 clades with similarity ranging between 85.53 to 100% and 98.28 to 100%, respectively, when compared within Thailand strain. Diversity analysis of sbp-2 and rap-1a sequences showed 18 and 4 haplotypes, respectively. The entropy analysis illustrated 104 and 7 polymorphic sites of sbp-2 and rap-1a nucleic acid sequences, respectively, while those of sbp-2 and rap-1a amino acid sequences showed 46 and 4 high entropy peaks, respectively. Motifs analysis exhibited the distribution and conservation among sbp-2 and rap-1a sequences. The continuous and discontinuous B-cell epitopes have also been evaluated in this work. Therefore, our findings may be used to ameliorate the understanding inputs of molecular phylogeny, genetic diversity and antigenicity of B. bovis and B. bigemina Thailand stains.

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“…Scientists, for example, Gimenez et al, claim that antigens against MSAs may block the invasion of blood cells and, consequently, protect the animal [ 78 ]. However, choosing proper domains of MSAs to maximize the efficacy of the vaccine still poses a problem that is being addressed by many teams worldwide [ 78 , 81 , 82 ]. Furthermore, it is suggested that treatment of GPI-anchor proteins with phospholipase C may reduce B. bovis merozoites’ ability for host cell invasion [ 18 , 83 ].…”

Section: Bovine Babesiosis Vaccinesmentioning

confidence: 99%

Advances in Babesia Vaccine Development: An Overview

et al. 2023

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Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. Since the current preventive measures against babesiosis are insufficient, there is increasing pressure to develop a vaccine. In this review, we survey the achievements and recent advances in the creation of antibabesiosis vaccine. The scope of this review includes the development of a vaccine against B. microti, B. bovis, B. bigemina, B. orientalis and B. divergens. Here, we present different strategies in their progress and evaluation. Scientists worldwide are still trying to find new targets for a vaccine that would not only reduce symptoms among animals but also prevent the further spread of the disease. Molecular candidates for the production of a vaccine against various Babesia spp. are presented. Our study also describes the current prospects of vaccine evolution for successful Babesia parasites elimination.

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Babesia bovis AMA-1, MSA-2c and RAP-1 contain conserved B and T-cell epitopes, which generate neutralizing antibodies and a long-lasting Th1 immune response in vaccinated cattle

Cited by 15 publications

References 37 publications

Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata

Spherical Body Protein 4 from Babesia bigemina: A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in Babesia ovata

Molecular characterization and genetic diversity of Babesia bovis and Babesia bigemina of cattle in Thailand

Advances in Babesia Vaccine Development: An Overview

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