RT Journal Article T1 Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc‑Spain7 in pregnant sheep at mid‑gestation A1 Sánchez Sánchez, Roberto A1 Ferré Pérez, Ignacio A1 Re, Michela Tatiana A1 Regidor Cerrillo, Javier A1 Blanco Murcia, Francisco Javier A1 Ferrer, Luis Miguel A1 Navarro, Teresa A1 Pizarro Díaz, Manuel A1 González Huecas, Marta A1 Tabanera De Lucio, Enrique A1 Benavides, Julio A1 Ortega Mora, Luis Miguel AB Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFNγ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFNγ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates. PB BioMed Central Ltd YR 2018 FD 2018 LK https://hdl.handle.net/20.500.14352/111896 UL https://hdl.handle.net/20.500.14352/111896 LA eng NO Sánchez-Sánchez, R., Ferre, I., Re, M. et al. Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation. Vet Res 49, 42 (2018). https://doi.org/10.1186/s13567-018-0539-5 NO JUSTIFICACIÓN DE AUTORES:IF, JB, JRC and LMO conceived the study and participated in its design. RSS wrote the manuscript, with results interpretation and discussion inputs from IF, MPD and LMO. LMF and TN selected the animals and carried out the reproductive programme. JRC prepared the inocula and carried out the infections. RSS, MR, JBM, MPD, MGH, ET and JB participated in inoculation, clinical examination and sampling of animals and performed necropsies and histopathological analyses. RSS performed PCR and qPCR analysis, serological assays, statistical analysis and interpreted the results. All authors read and approved the final manuscript. NO Ministerio de Educación, Cultura y Deportes (España) NO Ministerio de Economía y Competitividad (España) NO Comunidad de Madrid DS Docta Complutense RD 6 abr 2025