Vaccines against bovine babesiosis: where we are now and possible roads ahead

Florín-Christensen, Mónica; Suárez, Carlos E.; Rodríguez, Anabel Elisa; Flores, Daniela; Schnittger, Leonhard

doi:10.1017/s0031182014000961

Cited by 78 publications

(96 citation statements)

References 303 publications

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“…In contrast, exposure of Babesia -naive adult animals usually results in fatal acute disease [35]. Several vaccination procedures based on attenuated strains are available and commonly used as control methods to prevent acute Babesia infections in several countries [2,36]. Vaccination with live attenuated B .…”

Section: Introductionmentioning

confidence: 99%

Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

et al. 2016

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The Rhipicephalus microplus tick is a notorious blood-feeding ectoparasite of livestock, especially cattle, responsible for massive losses in animal production. It is the main vector for transmission of pathogenic bacteria and parasites, including Babesia bovis, an intraerythrocytic apicomplexan protozoan parasite responsible for bovine Babesiosis. This study describes the development and testing of a live B. bovis vaccine expressing the protective tick antigen glutathione-S-transferase from Haemaphysalis longicornis (HlGST). The B. bovis S74-T3B parasites were electroporated with a plasmid containing the bidirectional Ef-1α (elongation factor 1 alpha) promoter of B. bovis controlling expression of two independent genes, the selectable marker GFP-BSD (green fluorescent protein–blasticidin deaminase), and HlGST fused to the MSA-1 (merozoite surface antigen 1) signal peptide from B. bovis. Electroporation followed by blasticidin selection resulted in the emergence of a mixed B. bovis transfected line (termed HlGST) in in vitro cultures, containing parasites with distinct patterns of insertion of both exogenous genes, either in or outside the Ef-1α locus. A B. bovis clonal line termed HlGST-Cln expressing intracellular GFP and HlGST in the surface of merozoites was then derived from the mixed parasite line HlGST using a fluorescent activated cell sorter. Two independent calf immunization trials were performed via intravenous inoculation of the HlGST-Cln and a previously described control consisting of an irrelevant transfected clonal line of B. bovis designated GFP-Cln. The control GFP-Cln line contains a copy of the GFP-BSD gene inserted into the Ef-1α locus of B. bovis in an identical fashion as the HIGST-Cln parasites. All animals inoculated with the HlGST-Cln and GFP-Cln transfected parasites developed mild babesiosis. Tick egg fertility and fully engorged female tick weight was reduced significantly in R. microplus feeding on HlGST-Cln-immunized calves. Collectively, these data show the efficacy of a transfected HlGST-Cln B. bovis parasite to induce detectable anti-glutathione-S-transferase antibodies and a reduction in tick size and fecundity of R. microplus feeding in experimentally inoculated animals.

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Section: Introductionmentioning

confidence: 99%

Transfected Babesia bovis Expressing a Tick GST as a Live Vector Vaccine

et al. 2016

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“…The predominance of α-helix in MSA-2a 1 and MSA-2c may be essential to their functioning and is compatible with the predicted structures of the native proteins [14]. This fact could be important for vaccine development as thus far recombinant proteins produced in bacteria have failed to provide protection upon challenge when used as vaccines in cattle [2]. The recombinant MSA-2b protein showed a higher degree of a random secondary structure than the others.…”

Section: Discussionmentioning

confidence: 83%

“…In South America, the parasite is transmitted by the common cattle tick ( Rhipicephalus microplus ), and it is distributed mostly in the northeast and northwest of Argentina, in the south-central regions of Brazil, and in other tropical and subtropical regions around the world. From an economic point of view, bovine babesiosis is the most important disease of cattle that is transmitted by arthropods and constitutes a potential risk to more than 500 million cattle [1, 2]. Prospectively, an increased number of cattle will be at risk of bovine babesiosis due to predicted expansion of the vector’s habitat in response to global warming.…”

Section: Introductionmentioning

confidence: 99%

“…Erythrocytes that are parasitized by B. bovis are sequestered in brain capillaries, leading to ischemia and neurological shock. In untreated animals, the infection can rapidly lead to abortions and death [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

“…They are recommended for use in bovines under a year of age and generally provide effective protection. However, if live vaccines are administered to adult animals, clinical symptoms of babesiosis can develop and lead to death if an infected animal is not treated [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

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A recombinant multi-antigen vaccine formulation containing Babesia bovis merozoite surface antigens MSA-2a1, MSA-2b and MSA-2c elicits invasion-inhibitory antibodies and IFN-γ producing cells

et al. 2016

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Background Babesia bovis is a tick-transmitted protozoan hemoparasite and the causative agent of bovine babesiosis, a potential risk to more than 500 million cattle worldwide. The vaccines currently available are based on attenuated parasites, which are difficult to produce, and are only recommended for use in bovines under one year of age. When used in older animals, these vaccines may cause life-threatening clinical symptoms and eventually death. The development of a multi-subunit recombinant vaccine against B. bovis would be attractive from an economic standpoint and, most importantly, could be recommended for animals of any age. In the present study, recombinant ectodomains of MSA-2a1, MSA-2b and MSA-2c antigens were expressed in Pichia pastoris yeast as secreted soluble peptides.ResultsThe antigens were purified to homogeneity, and biochemically and immunologically characterized. A vaccine formulation was obtained by emulsifying a mixture of the three peptides with the adjuvant Montanide ISA 720, which elicited high IgG antibody titers against each of the above antigens. IgG antibodies generated against each MSA-antigen recognized merozoites and significantly inhibited the invasion of bovine erythrocytes. Cellular immune responses were also detected, which were characterized by splenic and lymph node CD4+ T cells producing IFN-γ and TNF-α upon stimulation with the antigens MSA-2a1 or MSA-2c.ConclusionsThese data strongly suggest the high protective potential of the presented formulation, and we propose that it could be tested in vaccination trials of bovines challenged with B. bovis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1862-1) contains supplementary material, which is available to authorized users.

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