Vaccination with an in vitro culture attenuated Babesia bovis strain safely protects highly susceptible adult cattle against acute bovine babesiosis

Authors: Bastos, Reginaldo; CAPELLI-PEIXOTO, JANAINA - Washington State University; LAUGHERY, JACOB - Washington State University; Suarez, Carlos; Ueti, Massaro

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2023
Publication Date: 7/31/2023
Citation: Bastos, R.G., Capelli-Peixoto, J., Laughery, J.M., Suarez, C.E., Ueti, M.W. 2023. Vaccination with an in vitro culture attenuated Babesia bovis strain safely protects highly susceptible adult cattle against acute bovine babesiosis. Frontiers in Immunology. 14. Article 1219913. https://doi.org/10.3389/fimmu.2023.1219913.
DOI: https://doi.org/10.3389/fimmu.2023.1219913

Interpretive Summary: Live in vivo attenuated Babesia bovis vaccines produced by sequential passages in splenectomized calves has been historically used to control acute bovine babesiosis in endemic areas worldwide. However, several constraints prevent the widespread use of these vaccines, including the need for several splenectomized calves to produce vaccine batches, and potential inconsistent parasite attenuation, which contraindicates the vaccine use for Babesia-highly susceptible adult cattle. Thus, the use of vaccines based on well-defined in vitro culture attenuated B. bovis strains emerges as a more sustainable and efficient alternative. Previous work demonstrated that the culture attenuated strain Att-S74-T3Bo is non-tick transmissible and able to safely protect young calves (<1 year of age) against needle challenge with a B. bovis virulent strain. In this study we evaluated the safety and the ablity of the culture attenuated strain Att-S74-T3Bo as a Babesia vaccine in adult animals. The results indicated that the vaccine causes self-limiting acute disease in vaccinated animals, while protected them from challenge with an homologous virulent B. bovis strain, that caused acute terminal disease in the non-vaccinated control animals which have to be all humanely euthanized. The study also included in depth analysis of the protective immune responses. Altogether, these emerging data also provided valuable information on the immune correlates of protection and the nature of protective immune responses against B. bovis that will be used for the future developing of alternative subunit vaccines. In conclusion, Att-S74-T3Bo emerges as an efficient and sustainable attenuated candidate vaccine strain to control acute bovine babesiosis in highly susceptible adult cattle. Future studies need to address the duration of immunity and efficacy of Att-S74-T3Bo against heterologous virulent parasite strains.

Technical Abstract: Live in vivo attenuated Babesia bovis vaccines produced by sequential passages in splenectomized calves has been historically used to control acute bovine babesiosis in endemic areas worldwide. However, several constraints prevent the widespread use of these vaccines, including the need for several splenectomized calves to produce vaccine batches, and potential inconsistent parasite attenuation, which contraindicates the vaccine use for Babesia-highly susceptible adult cattle. Thus, the use of vaccines based on well-defined in vitro culture attenuated B. bovis strains emerges as a more sustainable and efficient alternative. Previous work demonstrated that the culture attenuated strain Att-S74-T3Bo is non-tick transmissible and able to safely protect young calves (<1 year of age) against needle challenge with a B. bovis virulent strain. Herein we evaluated safety and efficacy of Att-S74-T3Bo in preventing acute babesiosis in adult (>1 year of age) cattle. Results demonstrated that Att-S74-T3Bo vaccination of adult animals (n=5) induced self-limiting signs of acute infection and protected the vaccinated animals against challenge with the homologous virulent B. bovis strain Vir-S74-T3Bo. Att-S74-T3Bo-vaccinated adult cattle developed significant (P<0.05) monocytosis, with concomitant neutropenia and CD4+ leukopenia, in peripheral blood early after vaccination. Also, vaccinated animals developed a specific signature of pro- and anti-inflammatory cytokine expression in peripheral blood and significant levels of IgM, total IgG, IgG1, and IgG2 against the B. bovis immunodominant antigen RAP-1 CT. Strikingly, none of the vaccinated animals showed any signs of acute babesiosis after challenge with Vir-S74-T3Bo. In contrast, control adult cattle (n=5) showed pathognomonic symptoms of acute babesiosis, and significant decrease (P<0.05) in lymphocytes, monocytes, and neutrophils, starting on day 7 post-challenge. All control animals developed severe acute babesiosis and were euthanized on days 10 through 12 days post-challenge. Thus, evidence from this study indicates that Att-S74-T3Bo is safe and protects highly susceptible adult cattle against challenge with a homologous virulent strain of B. bovis. In conclusion, Att-S74-T3Bo emerges as an efficient and sustainable attenuated candidate vaccine strain to control acute bovine babesiosis in highly susceptible adult cattle. Future studies need to address the duration of immunity and efficacy of Att-S74-T3Bo against heterologous virulent parasite strains.