Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand

Abstract Babesiosis is an economically important infectious disease affecting cattle worldwide. In order to longitudinally evaluate the humoral immune response against Babesia bovis and the merozoite surface antigen diversity of B. bovis among naturally infected calves in Taiaçu, Brazil, serum and DNA samples from 15 calves were obtained quarterly, from their birth to 12 months of age. Anti-B. bovis IgG antibodies were detected by means of the indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). The polymerase chain reaction (PCR) was used to investigate the genetic diversity of B. bovis, based on the genes that encode merozoite surface antigens (MSA-1, MSA-2b and MSA-2c). The serological results demonstrated that up to six months of age, all the calves developed active immunity against B. bovis. Among the 75 DNA samples evaluated, 2, 4 and 5 sequences of the genes msa-1, msa-2b and msa-2c were obtained. The present study demonstrated that the msa-1 and msa-2b genes sequences amplified from blood DNA of calves positive to B. bovis from Taiaçu were genetically distinct, and that msa-2c was conserved. All animals were serologically positive to ELISA and IFAT, which used full repertoire of parasite antigens in despite of the genetic diversity of MSAs.

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Diversity of Babesia bovis merozoite surface antigen genes in the Philippines

Parasitology International ◽

10.1016/j.parint.2013.09.003 ◽

2014 ◽

Vol 63 (1) ◽

pp. 57-63 ◽

Cited By ~ 12

Author(s):

Muncharee Tattiyapong ◽

Thillaiampalam Sivakumar ◽

Adrian Patalinghug Ybanez ◽

Rochelle Haidee Daclan Ybanez ◽

Zandro Obligado Perez ◽

...

Keyword(s):

Surface Antigen ◽

The Philippines ◽

Babesia Bovis ◽

Merozoite Surface Antigen

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The Babesia bovis Merozoite Surface Antigen 1 Hypervariable Region Induces Surface-Reactive Antibodies That Block Merozoite Invasion

Infection and Immunity ◽

10.1128/iai.00032-06 ◽

2006 ◽

Vol 74 (6) ◽

pp. 3663-3667 ◽

Cited By ~ 17

Author(s):

Tanya LeRoith ◽

Shawn J. Berens ◽

Kelly A. Brayton ◽

Stephen A. Hines ◽

Wendy C. Brown ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Surface Antigen ◽

Hypervariable Region ◽

Babesia Bovis ◽

Related Family ◽

Erythrocyte Invasion ◽

Merozoite Surface Antigen ◽

Carboxy Terminal ◽

Blocking Antibodies

ABSTRACT A hypervariable region (HVR) previously identified in the carboxy-terminal one-third of the Babesia bovis variable merozoite surface antigen family was more extensively analyzed in merozoite surface antigen 1 (MSA-1) from 16 strains and isolates. The MSA-1 HVR is proline rich and contains three semiconserved motifs nearly identical to those described for the related family member MSA-2. Two MSA-1-specific monoclonal antibodies previously shown to be reactive with the merozoite surface bound to a recombinant construct encoding the HVR, indicating that the HVR is surface exposed and accessible to antibody binding. Importantly, these surface-reactive, HVR-specific monoclonal antibodies were capable of inhibiting merozoite infectivity of the host erythrocyte in vivo. The results indicate that the MSA-1 HVR is involved in erythrocyte invasion and suggest that selection of MSA-1 variants may be driven by invasion-blocking antibodies.

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Persistence of Antibodies against Epitopes Encoded by a Single Gene Copy of the Babesia bovis Merozoite Surface Antigen 1 (MSA-1)

Journal of Parasitology ◽

10.2307/3284511 ◽

1998 ◽

Vol 84 (2) ◽

pp. 449 ◽

Cited By ~ 3

Author(s):

Terry F. McElwain ◽

Stephen A. Hines ◽

Guy H. Palmer

Keyword(s):

Surface Antigen ◽

Single Gene ◽

Babesia Bovis ◽

Gene Copy ◽

Merozoite Surface Antigen

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Merozoite Surface Antigen 2 Proteins of Babesia bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats

Infection and Immunity ◽

10.1128/iai.73.11.7180-7189.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7180-7189 ◽

Cited By ~ 48

Author(s):

Shawn J. Berens ◽

Kelly A. Brayton ◽

John B. Molloy ◽

Russell E. Bock ◽

Ala E. Lew ◽

...

Keyword(s):

Surface Antigen ◽

Protective Immunity ◽

Sequence Variation ◽

Immune Escape ◽

Hypervariable Region ◽

Babesia Bovis ◽

Erythrocyte Invasion ◽

Merozoite Surface Antigen ◽

Nucleotide Repeats ◽

Degenerate Nucleotide

ABSTRACT The merozoite surface antigen 2 (MSA-2) proteins of Babesia bovis are members of the variable merozoite surface antigen (VMSA) family that have been implicated in erythrocyte invasion and are important targets for antibody-mediated blocking of invasion. Extensive sequence variation in another VMSA member, MSA-1, has been shown in all vaccine breakthrough isolates. To test the hypothesis that the msa-2 genes of vaccine breakthrough isolates would also encode a diverse set of proteins, the complete msa-2 locus was characterized from 12 Australian B. bovis strains and isolates, including two vaccine strains and eight vaccine breakthrough isolates, and compared to the loci in previously and newly characterized American strains. In contrast to American strains, the msa-2 loci of all Australian strains and isolates examined contain, in addition to msa-2c, only a solitary gene (designated msa-2a/b) closely related to American strain msa-2a and msa-2b. Nevertheless, the proteins encoded by these genes are quite diverse both between and within geographic regions and harbor evidence of genetic exchange among other VMSA family members, including msa-1. Moreover, all but one of the Australian breakthrough isolate MSA-2a/b proteins is markedly different from the vaccine strain from which immune escape occurred, consistent with their role in strain-specific protective immunity. The densest distribution of polymorphisms occurs in a hypervariable region (HVR) within the carboxy third of the molecule that is highly proline rich. Variation in length and content of the HVR is primarily attributable to differences in the order and number of degenerate nucleotide repeats encoding three motifs of unknown function.

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Surface epitope localization and gene structure of a Babesia bovis 44-kilodalton variable merozoite surface antigen

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(92)90128-7 ◽

1992 ◽

Vol 55 (1-2) ◽

pp. 75-84 ◽

Cited By ~ 39

Author(s):

Douglas P. Jasmer ◽

David W. Reduker ◽

Stephen A. Hines ◽

Lance E. Perryman ◽

Travis C. McGuire

Keyword(s):

Surface Antigen ◽

Gene Structure ◽

Babesia Bovis ◽

Merozoite Surface Antigen

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Genetic Diversity of Babesia bovis MSA-1, MSA-2b and MSA-2c in China

Pathogens ◽

10.3390/pathogens9060473 ◽

2020 ◽

Vol 9 (6) ◽

pp. 473

Author(s):

Jinming Wang ◽

Jifei Yang ◽

Shandian Gao ◽

Xiaoxing Wang ◽

Hao Sun ◽

...

Keyword(s):

Genetic Diversity ◽

Immune Responses ◽

Nested Pcr ◽

Phylogenetic Analyses ◽

Apicomplexan Parasite ◽

Amino Acid Sequences ◽

Babesia Bovis ◽

Chain Reaction ◽

Merozoite Surface Antigen ◽

Polymerase Chain

The apicomplexan parasite Babesia bovis is a tick-borne intracellular hemoprotozoan parasite that is widespread across China. Genetic diversity is an important strategy used by parasites to escape the immune responses of their hosts. In our present study, 575 blood samples, collected from cattle in 10 provinces, were initially screened using a nested PCR (polymerase chain reaction) for detection of B. bovis infection. To perform genetic diversity analyses, positive samples were further amplified to obtain sequences of three B. bovis merozoite surface antigen genes (MSA-1, MSA-2b, MSA-2c). The results of the nested PCR approach showed that an average of 8.9% (51/575) of cattle were positive for B. bovis infection. Phylogenetic analyses of the predicted amino acid sequences revealed that unique antigen variants were formed only by Chinese isolates. Our findings provide vital information for understanding the genetic diversity of B. bovis in China.

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

Infection and Immunity ◽

10.1128/iai.73.9.5388-5394.2005 ◽

2005 ◽

Vol 73 (9) ◽

pp. 5388-5394 ◽

Cited By ~ 36

Author(s):

Tanya LeRoith ◽

Kelly A. Brayton ◽

John B. Molloy ◽

Russell E. Bock ◽

Stephen A. Hines ◽

...

Keyword(s):

Vaccine Strain ◽

Surface Antigen ◽

Sequence Variation ◽

Antigenic Variation ◽

Cross Reactivity ◽

Babesia Bovis ◽

Extracellular Region ◽

Merozoite Surface Antigen ◽

The Difference ◽

Blocking Antibodies

ABSTRACT 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.

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