Babesia bovis AMA-1, MSA-2c and RAP-1 contain conserved B and T-cell epitopes, which generate neutralizing antibodies and a long-lasting Th1 immune response in vaccinated cattle

Authors: HIDALGO-RUIZ, MANUEL - Autonomous University Of Queretaro; MEJIA-LÓPEZ, SUSANA - Autonomous University Of Queretaro; PEREZ-SERRANO, ROSA - Autonomous University Of Queretaro; ZALDÍVAR-LELO DE LAR, REA GUADALUPE - Autonomous University Of Queretaro; GANZINELLI, SABRINA - Instituto De Clima Y Agua (INTA); FLORIN-CHRISTENSEN, MONICA - Instituto De Clima Y Agua (INTA); Suarez, Carlos; HERNÁNDEZ-ORTIZ, RUBEN - Instituto Nacional De Investigaciones Forestales Y Agropecuarias (INIFAP); MERCADO-URIOSTEGUI, MIGUAL - Autonomous University Of Queretaro; RODRÍGUEZ-TORRES, AXANA - Autonomous University Of Queretaro; CARVAJAL-GAMEZ, BERTHA - Autonomous University Of Queretaro; CAMACHO-NUEZ, MINERVA - Autonomous University Of Queretaro; WILKOWSKY, SILVINA - Autonomous National University Of Mexico; MOSQUEDA, JUAN - Autonomous University Of Queretaro

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/13/2022
Publication Date: 1/22/2022
Citation: Hidalgo-Ruiz, M., Mejia-López, S., Perez-Serrano, R.M., Zaldívar-Lelo de Larrea, R., Ganzinelli, S., Florin-Christensen, M., Suarez, C.E., Hernández-Ortiz, R., Mercado-Uriostegui, M.A., Rodríguez-Torres, A., Carvajal-Gamez, B.I., Camacho-Nuez, M., Wilkowsky, S.E., Mosqueda, J. 2022. Babesia bovis AMA-1, MSA-2c and RAP-1 contain conserved B and T-cell epitopes, which generate neutralizing antibodies and a long-lasting Th1 immune response in vaccinated cattle. Vaccine. 40(8):1108-1115. https://doi.org/10.1016/j.vaccine.2022.01.023.
DOI: https://doi.org/10.1016/j.vaccine.2022.01.023

Interpretive Summary: It is known that, to be effective, vaccines against bovine babesiosis must induce strong humoral immune response characterized by neutralizing antibodies against conserved epitopes and lon-lasting cellular immune responses. In this study, we identified peptides of three Babesia bovis antigens (termed AMA-1, MSA-2c, and RAP-1) that elicit such required neutralizing and long-lasting cellular immune responses. However, in vitro testing of several peptide candidates from each of these proteins, strongly suggests that different selected peptides from the same protein can elicit distinct immune responses, a finding that has implication for vaccine development in bovine babesiosis.

Technical Abstract: Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis, proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro: P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 + / CD45RO + T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN- ) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis.