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. 2021 Dec 9;10(12):1598.
doi: 10.3390/pathogens10121598.

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

Naomi S Taus  1 , Colette Cywes-Bentley  2 , Wendell C Johnson  1 , Gerald B Pier  2 , Lindsay M Fry  1   3 , Michelle R Mousel  1   4 , Massaro W Ueti  1   3   4
Affiliations
Free PMC article

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

Naomi S Taus et al. Pathogens. .
Free PMC article

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.

Keywords: Babesia; PNAG; Rhipicephalus ticks; antibody response; immunization.

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Conflict of interest statement

Gerald B. Pier is an inventor of intellectual properties (human monoclonal antibody to PNAG and PNAG vaccines) that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC, entities in which GBP also holds equity. As an inventor of intellectual properties, GBP also has the right to receive a share of licensing-related income (royalties, fees) through the Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. GBP’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Partners Health care in accordance with their conflict of interest policies. Colette Cywes-Bentley is an inventor of intellectual properties (use of human monoclonal antibody to PNAG and use of PNAG vaccines) that are licensed by the Brigham and Women’s Hospital to Alopexx Pharmaceuticals, LLC. As an inventor of intellectual properties, CC-B also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC.

Figures

Figure 1
Figure 1
Conservation of poly-N-acetyl-glucosamine (PNAG) in Babesia spp. demonstrated using direct immunofluorescence on infected blood smears. DNA stain = Babesia DNA detected using SYTO 83; αPNAG = Alexafluor 488-conjugated anti-PNAG monoclonal antibody; phase contrast = light micrograph; merge = merged image of panels DNA stain and αPNAG columns. White bars = 10 µm.
Figure 2
Figure 2
Stimulation of PNAG-specific antibodies following immunization with 5GlcNH2-TT plus adjuvant (light bars) vs. adjuvant only group (dark bars). p < 0.001, ANOVA.
Figure 3
Figure 3
Recognition of B. bovis blood stages by sera from immunized cattle demonstrated using indirect immunofluorescence. Each set of four panels arranged starting at upper left going clockwise are SYTO 83 DNA stain, calf serum, merged image, phase contrast. (A) Reactivity of sera from control calves with thin blood smears of B. bovis-infected red blood cells. (B) Reactivity of sera from 5GlcNH2-TT-immunized calves with thin blood smears of B. bovis-infected red blood cells. Arrow heads in C1590 Post indicate parasite without serum reactivity. Arrows in C1594 Post indicate serum reactivity without DNA staining. Closed arrows in C1595 indicate co-localization of DNA stain and serum reactivity. Pre = Pre-immune sera; Post = sera 72d post-immunization. White bars are 10 µm.
Figure 4
Figure 4
Opsonophagocytic killing of Staphylococcus aureus MN8 by sera 35d post vaccination. * p < 0.001, Student’s t-test.
Figure 5
Figure 5
Detection of B. bovis-infected erythrocytes in the capillaries of the (A) cerebrum and (B) midbrain of an adjuvant-only control calf (Control) and a PNAG-immunized calf (Immunized) challenged with B. bovis. Arrows indicate B. bovis-infected erythrocytes. Images are representative of all calves.
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