Evaluation of different heterologous prime–boost immunization strategies against Babesia bovis using viral vectored and protein-adjuvant vaccines based on a chimeric multi-antigen

Ortiz, José Manuel Jaramillo; Molinari, María Paula; Gravisaco, Marí­a José; Paoletta, Martina Soledad; Montenegro, Valeria Noely; Wilkowsky, Silvina Elizabeth

doi:10.1016/j.vaccine.2016.05.053

Cited by 18 publications

(12 citation statements)

References 32 publications

(44 reference statements)

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“…We hypothesized that after Babesia invades erythrocytes, B and T cells of the host may yield a protective immune response, which is similar to pathways of resistance to Plasmodium parasites. Recently, one study has described the protection elicited by MSA-derived vaccines from B. bovis and has shown that the anti- Babesia activity is due to CD4+ and CD8+ T cells (Gimenez et al, 2016b ; Jaramillo Ortiz et al, 2016 ). In the present study, this protozoa's BMSA has been identified as an effector molecule that resulted in Th2 cytokines being secreted and contributing to BMSA-mediated protection in immunized BALB/c mice.…”

Section: Discussionmentioning

confidence: 99%

“…In the host, these proteins are targeted by the humoral immune response or they activate a T-effector cell response (Hines et al, 1995 ; Suarez et al, 2000 ). The surface proteins present in early transcribed membrane proteins of B. microti include the merozoite surface antigens, the variable merozoite surface antigen family, and the rhoptry-associated proteins (Hines et al, 1995 ; Suarez et al, 2000 ; Mosqueda et al, 2002a , b ; Jaramillo Ortiz et al, 2016 ). Such surface antigens may be useful for developing a diagnostic test for babesiosis as well as a vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

Man¹,

Fu²,

Guan³

et al. 2017

Front. Microbiol.

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Babesia species are tick-borne intraerythrocytic protozoa that cause babesiosis in humans worldwide. No vaccine has yet proven effective against Babesia infection. Surface antigens of merozoites are involved in the invasion of erythrocytes by Babesia. Surface antigens may be presented by both babesial sporozoites and merozoites and provide a general target for antibody-mediated inhibition of erythrocyte invasion. Here we evaluated a major surface antigen of B. microti merozoites, BMSA, as a potential vaccine to prevent babesiosis. Our data indicated that bmsa is transcribed during different phases, including ring form, amoeboid form, and merozoites, and that its expression is significantly increased in mature merozoites. The protein was found to be located in the membrane of B. microti and in the cytoplasm of infected erythrocytes. The immune response induced by BMSA had a significant inhibitory effect on parasite invasion of the host erythrocytes (83.3% inhibition of invasion) and parasite growth in vivo. The levels of parasitemia significantly decreased after BMSA vaccination when mice were infected with babesia parasite. Importantly, protective immunity was significantly related to the upregulation of the Th17 cytokine interleukin-17, the Th1 cytokine interleukin-12p70 and the Th2 cytokines, such as interleukin-4, -6, and -10. Ingenuity Pathway Analysis indicated that interleukin-17 facilitated the secretion of Th2 cytokines, such as interleukin-10, -4, and -6, thereby inducing a predominately Th2 protective immune response and promoting the expression a high level of special IgG1 against Babesia infection. Further, an anti-BMSA monoclonal antibody successfully protected NOD/SCID mice from a challenge with B. microti. Taken together, our results indicated that BMSA induces a protective immune response against Babesia infection and may serve as a potential vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

Man¹,

Fu²,

Guan³

et al. 2017

Front. Microbiol.

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“…In this work, we have developed an iELISA based on a chimeric polyprotein comprising the immunodominant regions of three B. bovis antigens, optimizing the display of multiple B cell epitopes in only one protein. In our previous work, we had observed that all samples of a small group of sera from B. bovis naturally-infected bovines recognized the rMABbo in western blots, whereas sera from non-infected cattle did not react [ 10 ]. These results led us to move a step further and assay this protein as a detection antigen in an iELISA format.…”

Section: Discussionmentioning

confidence: 99%

“…In order to obtain the rMABbo, the fragments of msa-2c , rap-1 and hsp20 (GenBank AY052542.1, AF030062.1, and AF331455.1, respectively) were firstly amplified by PCR and sequentially ligated into a pCR ® 8/GW-TOPO ® TA Gateway cloning kit vector (Invitrogen Corp, Carlsbad, CA, USA). Then, the single genetic sequence encoding the rMABbo was transferred directionally into pDEST 17™ vector and expressed in E. coli strain BL21 AI™ (both from Invitrogen) as previously described [ 10 ]. The rMABbo contains a 6X Histidine tag and was purified under denaturing conditions with a Ni-Agarose resin (Probond, Invitrogen) according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…In this work we evaluated the performance of an iELISA using a novel chimerical multi-antigen previously developed in our laboratory [ 10 ]. This recombinant multi-antigen (rMABbo) was developed as a vaccine candidate and comprises gene fragments with B and T cell epitopes of three B. bovis antigens: MSA-2c, RAP-1 and the Heat Shock protein 20.…”

Section: Introductionmentioning

confidence: 99%

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Development of an Indirect ELISA Based on a Recombinant Chimeric Protein for the Detection of Antibodies against Bovine Babesiosis

Ortiz

Montenegro

Fourniere

et al. 2018

Veterinary Sciences

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The current method for Babesia spp. serodiagnosis based on a crude merozoite antigen is a complex and time-consuming procedure. An indirect enzyme-linked immunosorbent assay (iELISA) based on a recombinant multi-antigen of Babesia bovis (rMABbO) was developed for detection of antibodies in bovines suspected of infection with this parasite. The multi-antigen comprises gene fragments of three previously characterized B. bovis antigens: MSA-2c, RAP-1 and the Heat Shock protein 20 that are well-conserved among geographically distant strains. The cutoff value for the new rMABbo-iELISA was determined using 75 known—positive and 300 known—negative bovine sera previously tested for antibodies to B. bovis by the gold-standard ELISA which uses a merozoite lysate. A cutoff value of ≥35% was determined in these samples by receiver operator characteristic (ROC) curve analysis, showing a sensitivity of 95.9% and a specificity of 94.3%. The rMABbo-iELISA was further tested in a blind trial using an additional set of 263 field bovine sera from enzootic and tick-free regions of Argentina. Results showed a good agreement with the gold standard test with a Cohen’s kappa value of 0.76. Finally, the prevalence of bovine babesiosis in different tick enzootic regions of Argentina was analyzed where seropositivity values among 68–80% were obtained. A certain level of cross reaction was observed when samples from B. bigemina infected cattle were analyzed with the new test, which can be attributed to shared epitopes between 2 of the 3 antigens. This new rMABbo-iELISA could be considered a simpler alternative to detect anti Babesia spp. antibodies and appears to be well suited to perform epidemiological surveys at the herd level in regions where ticks are present.

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Babesia in Domestic Ruminants

Ganzinelli

Rodríguez

Schnittger

et al. 2017

Parasitic Protozoa of Farm Animals and Pets

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Evaluation of different heterologous prime–boost immunization strategies against Babesia bovis using viral vectored and protein-adjuvant vaccines based on a chimeric multi-antigen

Cited by 18 publications

References 32 publications

Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

Development of an Indirect ELISA Based on a Recombinant Chimeric Protein for the Detection of Antibodies against Bovine Babesiosis

Babesia in Domestic Ruminants

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