2026-06-29T08:15:41Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1367802026-05-20T00:06:18Zcom_20.500.14352_14col_20.500.14352_15

BKI-1748 confers a high level of protection against ovine congenital toxoplasmosis when administered after IgM seroconversion Sánchez Sánchez, Roberto Velasco Jiménez, Natalia Arranz Solís, David Criado, Miguel Ferré Pérez, Ignacio Re, Michela Tatiana Hulverson, Matthew A. Choi, Ryan Barrett, Lynn K. Hemphill, Andrew Van Voorhis, Wesley C. Ortega Mora, Luis Miguel 636.09 BKI-1748 Congenital toxoplasmosis Efficacy IgM Sheep Toxoplasma gondii, Translational pharmaceutics Veterinaria 3109 Ciencias Veterinarias Author contributions RS-S: Conceptualization, Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing. NV-J: Investigation, Methodology, Writing – review & editing. DA-S: Investigation, Writing – review & editing. MC: Investigation, Writing – review & editing. IF: Investigation, Writing – review & editing. MR: Investigation, Writing – review & editing. MH: Conceptualization, Investigation, Writing – review & editing. RC: Conceptualization, Investigation, Writing – review & editing. LB: Investigation, Writing – review & editing. AH: Conceptualization, Funding acquisition, Writing – review & editing. WV: Conceptualization, Funding acquisition, Project administration, Writing – review & editing. L-MO-M: Conceptualization, Funding acquisition, Project administration, Supervision, Writing – review & editing Background: Unlike mouse models of congenital toxoplasmosis, pregnant sheep models provide the opportunity to evaluate treatment strategies that more closely resemble clinical practice in pregnant women, including chemotherapeutic interventions initiated after specific IgM seroconversion. BKI-1748, which targets Toxoplasma gondii CDPK1 and MAPKL-1 protein kinases, has demonstrated an excellent safety profile and efficacy when administered repeatedly to pregnant sheep, starting at 2 and 7 days after challenge Methods: In this study, treatment was initiated at day 14 post-infection (p.i.), following T. gondii IgM seroconversion. Twenty-three sheep were orally inoculated with 10 TgShSp1 oocysts at 90 days of gestation, while three sheep remained uninfected. On day 14 p.i., infected sheep carrying live fetuses (n = 10) received 10 doses of BKI-1748 orally at 15 mg/kg every 2 days, whereas 10 infected sheep were left untreated. Results: All infected sheep, both treated and untreated, seroconverted to serum IgG by day 21 p.i., with treated sheep showing a marked reduction in IgG levels from day 28 p.i. onward. Administration of the compound significantly enhanced lamb viability in infected sheep, resulting in 91% viable lambs in treated animals compared to 52% in untreated sheep. Whereas all lambs born to untreated sheep were congenitally infected, only 17% of lambs in the treated group were infected. Nevertheless, congenitally infected lambs in the treated group had lower birth weights than T. gondii-free lambs. Conclusion: This study highlights the potential utility of BKI-1748 for prenatal treatment of human congenital toxoplasmosis, in which IgM seroconversion prompts the need for intervention. United States Department of Agriculture National Institutes of Health (USA) Swiss National Science Foundation Comunidad de Madrid Depto. de Sanidad Animal Depto. de Medicina y Cirugía Animal Fac. de Veterinaria TRUE pub 2026-05-19T16:18:12Z 2026-05-19T16:18:12Z 2026 journal article VoR https://hdl.handle.net/20.500.14352/136780 XXXX-XXXX 10.3389/fcimb.2026.1819490 2235-2988 eng 2020-67015-30881 R01 HD102487 310030_214897 TEC−2024/BIO−66/SALAINDEC−CM Sánchez-Sánchez R, Velasco-Jiménez N, Arranz-Solís D, Criado M, Ferre I, Re M, Hulverson MA, Choi R, Barrett LK, Hemphill A, Van Voorhis WC and Ortega-Mora LM (2026) BKI-1748 confers a high level of protection against ovine congenital toxoplasmosis when administered after IgM seroconversion. Front. Cell. Infect. Microbiol. 16:1819490. doi: 10.3389/fcimb.2026.1819490 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf Frontiers Media