Table 3 Promising vaccine development studies and their prospects

Live attenuated

[25]

The absence of significant changes in immune cell behavior and cytokine expression patterns in animals infected with Att-S74-T3Bo and then superinfected with Vir-S74-T3Bo suggests that antibodies might play a role in providing protection during reinfection

• In future vaccine trials, it is recommended to prioritize certain approaches such as using live attenuated parasites, genetically modified live parasites, Babesia antigens, and novel adjuvants

• These methods should focus on activating myeloid cells (monocytes and neutrophils) and CD4⁺ T cells early on. It is also important to assess the balance of pro- and regulatory cytokines (TNF-α, CXCL10, IFN-γ, IL-10, and IL-4) in the peripheral blood as a potential indicator of protection against acute Babesia infection

Subunit

[21]

Despite using peptides of B. bovis antigens in vaccines that generate neutralizing immunity and involve CD4⁺ T cells, the resulting Th1 immune response was not effective in protecting vaccinated cattle against a virulent strain of B. bovis. This failure may be due to using a single antigen in the vaccine, which may not generate a strong enough immune response to block multiple stages of the invasion process

• In this research, the scientists discovered peptides of MSA2c and AMA-1 that could generate neutralizing antibodies and IFN-γ, which is a Th1 cytokine associated with protection

• However, it remains to be determined whether a combination of these peptides in a multi-antigen vaccine could enhance the effectiveness of the immune response, in terms of both humoral and cellular responses, or during exposure to a virulent strain

Subunit

[19]

Different B. bovis strains that significantly hinder the effectiveness of live vaccines and pose a challenge in creating subunit vaccines

• Considering that BbAMA-1's structural domains I and II can elicit both humoral and cellular immune responses, especially Th1 responses, BbAMA-1 is a promising vaccine candidate for bovine babesiosis

• This is significant because strain variations pose challenges to live vaccines and subunit vaccine development. BbAMA-1, being highly conserved, has the potential to overcome strain-related issues by providing protective immunity against various B. bovis strains in real-world conditions

Subunit

[7]

It is worth noting that B. bovis may not have all the necessary enzymes for complete N-linked glycosylation, unlike the Plasmodium parasite. As a result, the native 6cys proteins in B. bovis are expected to differ in terms of protein folding, surface glycan profile, stability, and other characteristics compared to recombinant 6cys proteins that undergo significant glycosylation when expressed in HEK 293 cells, which is a eukaryotic system

• Peptides derived from B. bovis cys proteins that were used to generate rabbit antibodies may provide protective epitopes

• As a result, future research efforts will be directed towards further investigating these specific regions of the 6cys A and 6cys B proteins to gain deeper insights into their immunogenicity and potential for protective immunity