Table 2 Vaccine strategies developed against B. bovis

Live attenuated

B. bovis-attenuated S74 T3Bo strain

New alterations in the composition of immune cells in the bloodstream, as well as changes in the expression of cytokines, have been observed in peripheral blood. These changes are linked to the immune response against acute bovine babesiosis and are indicative of a protective effect

[25]

Subunit

B. bovis apical membrane antigen 1 (AMA-1), merozoite surface antigen 2c (MSA-2c), and rhoptry-associated protein 1 (RAP-1) proteins

AMA-1, MSA-2c, and RAP-1 contain conserved epitopes that are recognized by B and T cells. These epitopes trigger the production of neutralizing antibodies and promote a durable Th1 immune response

[21]

Subunit

Structural ectodomains I and II of B. bovis apical membrane antigen 1 [BbAMA-1(I/II)]

Cattle that have been immunized with BbAMA-1(I/II) exhibit substantially elevated levels of total immunoglobulin (Ig)G antibodies, along with a heightened ratio of IgG2 to IgG1. Furthermore, this immunization has been found to induce a robust Th1 cell response in the vaccinated cattle

[19]

Live attenuated

Stable transfected strain of B. bovis expressing an enhanced green fluorescent protein (eGFP) and a chimeric version of Bm86 (B. bovis/Bm86/eGFP)

Post-mortem analysis did not reveal any indication of parasites sequestering in the cerebral capillaries, which confirms that the strain has been attenuated. Additionally, this is the first documented case of B. bovis that has been genetically modified to express the tick antigen Bm86 on the surface of merozoites, triggering an antibody response against native Bm86

[26]

Subunit

Synthetic ß-(1 → 6)-linked glucosamine oligosaccharides conjugated to tetanus toxoid (5GlcNH₂-TT)

Experienced acute babesiosis, characterized by the adherence of infected erythrocytes to capillary vessels in the brain. Despite the production of antibodies against this antigen, they were unable to prevent the onset of the disease

[24]

Subunit

B. bovis 6-cysteine proteins A and B

Cattle that were immunized produced antibodies against r6cys A and r6cys B, but these antibodies were ineffective in inhibiting the sexual reproduction of the parasite in ticks

[7]

Subunit

B. bovis GPI-anchored surface antigen 1 (GASA-1)

When B. bovis in vitro cultures were exposed to anti-GASA-1 antibodies, there was a partial yet significant reduction in erythrocyte invasion. This suggests that the protein GASA-1 contains epitopes that are sensitive to neutralization by antibodies

[20]

Viral vector

B. bovis merozoite surface antigen 2c (MSA-2c), rhoptry-associated protein 1 (RAP-1), and heat shock protein 20 (HSP20)

The absence of protective effects observed with this recombinant formulation underscores the importance of conducting additional basic and clinical investigations in the bovine model to attain the desired level of effectiveness

[27]

Subunit

B. bovis rhoptry neck protein 2 (RON2)

RON2 as a novel B. bovis vaccine candidate antigen that contains conserved B-cell epitopes that elicit partially neutralizing antibodies

[22]

Subunit

B. bovis merozoite surface antigens (MSA-1, MSA-2b, and MSA-2c)

Calves up to 6 months of age, all the calves developed active immunity against B. bovis

[23]

Subunit

B. bovis merozoite surface antigens: MSA-2a1, MSA-2b, and MSA-2c

Elicited invasion-inhibitory antibodies and IFN-γ-producing cells

[18]

Viral vector

Chimeric multi-antigen of DNA fragments containing B- and T-cell epitopes of merozoite surface antigen 2c (MSA-2c), rhoptry-associated protein 1 (RAP-1) and heat shock protein 20 (HSP20) genes

Elevated levels of IgG, IFN-γ, CD4⁺ and CD8⁺ T cells were successfully attained

[28]

Viral vector

Immunodominant B- and T-cell epitopes of three B. bovis proteins: merozoite surface antigen 2c (MSA-2c), rhoptry-associated protein 1 (RAP-1), and heat shock protein 20 (HSP20)

The viral-vectored approach alone induced significant levels of IFN-γ and resulted in a higher ratio of IgG2a subclass

[29]