Investigations of breakdowns in protection provided by living Babesia bovis vaccine

Bock, R.E.; Vos, A.J. De; Kingston, T G; Shiels, Ian A.; Dalgliesh, R.J.

doi:10.1016/0304-4017(92)90047-d

Cited by 72 publications

(62 citation statements)

References 17 publications

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“…Parasites were grown in long-term microaerophilic stationary-phase culture by previously described techniques (17). Attenuated B. bovis K and T strains were attained by serial passage through splenectomized calves as previously described (2,3). Vaccine breakthrough isolates were obtained from cattle vaccinated with the T or K strains that subsequently were diagnosed with clinical babesiosis.…”

Section: Methodsmentioning

confidence: 99%

“…Vaccine breakthrough isolates were obtained from cattle vaccinated with the T or K strains that subsequently were diagnosed with clinical babesiosis. The isolates were then passaged once through splenectomized calves as described previously (2). Outbreak isolates from animals immunized with the T vaccine were designated as G isolates (n ϭ 8), and those from animals immunized with the K vaccine as E and F isolates (n ϭ 6) (2, 3).…”

Section: Methodsmentioning

confidence: 99%

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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

LeRoith

Brayton

Molloy³

et al. 2005

Infect Immun

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

LeRoith

Brayton

Molloy³

et al. 2005

Infect Immun

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“…Although attenuated vaccines generally provide protection against bovine babesiosis, disease outbreaks involving heterologous isolates occur (4,5). These heterologous field isolates, termed vaccine breakthrough isolates, are genetically distinct from the vaccine strain used to immunize animals (13).…”

mentioning

confidence: 99%

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

Berens

Brayton

Molloy³

et al. 2005

Infect Immun

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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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“…The selection of antigenically distinct populations was probably responsible for the babesiosis outbreaks by B. bovis in cattle immunized with attenuated organisms of the Australian Ka clone (Bock et al 1992). This is an indication that the antigenic variation is a mechanism for Babesia evasion of the host's immune system.…”

Section: Monoclonal Antibodies Monoclonal Antibodies Monoclonal Antibmentioning

confidence: 99%

“…The importance of first ones is demonstrated by the heterologous protection given by live attenuated vaccine, or immunization with dead organisms, native and recombinant proteins (Wright et al 1992, Callow et al 1997. On the other hand, the babesiosis outbreaks after a long period of cattle vaccination with B. bovis Ka clone (Bock et al 1992) suggest that babesia organisms have mechanisms of immune evasion. Based on the data obtained with the genetic and antigenic analysis of the Brazilian B. bigemina isolates and in the present knowledge of some antigens and immune response, it is possible to visualize a logical approach for antigen selection to compose a subunit vaccine.…”

Section: Monoclonal Antibodies Monoclonal Antibodies Monoclonal Antibmentioning

confidence: 99%

Genetic and antigenic analysis of Babesia bigemina isolates from five geographical regions of Brazil

et al. 2002

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A molecular epidemiological study was performed with Babesia bigemina isolates from five geographical regions of Brazil. The genetic analysis was done with random amplification of polymorphic DNA (RAPD), repetitive extragenic palindromic elements-polymerase chain reaction (REP-PCR) and enterobacterial repetitive intergenic consensus sequences-polymerase chain reaction (ERIC-PCR) that showed genetic polymorphism between these isolates and generated fingerprinting. In RAPD, ILO872 and ILO876 primers were able to detect at least one fingerprinting for each B. bigemina isolate. The amplification of B. bigemina DNA fragments by REP-PCR and ERIC-PCR gave evidence for the presence in this haemoprotozoan of the sequences described previously in microorganisms of the bacterial kingdom. For the first time it was demonstrated that both techniques can be used for genetic analysis of a protozoan parasite, although the ERIC-PCR was more discriminatory than REP-PCR. The dendogram with similarity coefficient among isolates showed two clusters and one subcluster. The Northeastern and Mid-Western isolates showed the greatest genetic diversity, while the Southeastern and Southern isolates were the closest. The antigenic analysis was done through indirect fluorescent antibody technique and Western blotting using a panel of monoclonal antibodies directed against epitopes on the merozoite membrane surface, rhoptries and membrane of infected erythrocytes. As expected, the merozoite variable surface antigens, major surface antigen (MSA)-1 and MSA-2 showed antigenic diversity. However, B cell epitopes on rhoptries and infected erythrocytes were conserved among all isolates studied. In this study it was possible to identify variable and conserved antigens, which had already been described as potential immunogens. Considering that an attenuated Babesia clone used as immunogen selected populations capable of evading the immunity induced by this vaccine, it is necessary to evaluate more deeply the cross-protection conferred by genetically more distant Brazilian B. bigemina isolates and make an evaluation of the polymorphism degree of variable antigens such as MSA-1 and MSA-2.INDEX TERMS: Babesia bigemina, Brazilian isolates, genetic polymorphism, antigenic polymorphism.

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Investigations of breakdowns in protection provided by living Babesia bovis vaccine

Cited by 72 publications

References 17 publications

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

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

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

Genetic and antigenic analysis of Babesia bigemina isolates from five geographical regions of Brazil

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