Immunization against a Conserved Surface Polysaccharide Stimulates Bovine Antibodies with Opsonic Killing Activity but Does Not Protect against Babesia bovis Challenge

Abstract

Arthropod-borne apicomplexan pathogens remain a great concern and challenge for disease control in animals and humans. In order to prevent Babesia infection, the discovery of antigens that elicit protective immunity is essential to establish approaches to stop disease dissemination. In this study, we determined that poly-N-acetylglucosamine (PNAG) is conserved among tick-borne pathogens including B. bovis, B. bigemina, B. divergens, B. microti, and Babesia WA1. Calves immunized with synthetic ß-(1→6)-linked glucosamine oligosaccharides conjugated to tetanus toxoid (5GlcNH2-TT) developed antibodies with in vitro opsonophagocytic activity against Staphylococcus aureus. Sera from immunized calves reacted to B. bovis. These results suggest strong immune responses against PNAG. However, 5GlcNH2-TT-immunized bovines challenged with B. bovis developed acute babesiosis with the cytoadhesion of infected erythrocytes to brain capillary vessels. While this antigen elicited antibodies that did not prevent disease, we are continuing to explore other antigens that may mitigate these vector-borne diseases for the cattle industry.

Exploring the landscape of Babesia bovis vaccines: progress, challenges, and opportunities

“…Most studies included in our systematic review reported the development of subunit vaccines (Fig. 3 C, Table 2 ) [ 7 , 18 – 24 ]. These subunit vaccines consisted of B. bovis membrane proteins, oligosaccharides, and merozoite surface antigens.…”

“…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 (5GlcNH 2 -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 <...…”