Immunogenicity, security and protection against small ruminant lentivirus (SRLV) challenge in sheep, induced by intranasal immunization with a recombinant Sendai virus vector expressing SRLV gag-P25

Small ruminant lentiviruses (SRLV) are responsible for significant economic losses in sheep and goat farming; however, effective vaccination strategies remain unavailable. This study evaluated the immunogenicity, safety, and protective efficacy of a recombinant Sendai virus vector (SeV) expressing SRLV gag-P25 (rSeV-GFP-P25) in lambs. Twenty-one SRLV-negative lambs were divided into three groups and inoculated intranasally thrice with culture medium (group 1); SeV-GFP (group 2) or rSeV-GFP-P25 (group 3). Lambs were challenged with homologous SRLV at 16 weeks post-first immunization. Clinical and hematological parameters, antibody responses, SRLV viral loads in peripheral blood mononuclear cells (PBMCs) and target tissues, histopathological and histomorphometric analyses, assisted with artificial intelligence, of interstitial pneumonia were assessed. No clinicopathological alterations were observed, except for a transient temperature increase in group 3 post-first immunization. Group 2 showed mild SeV-neutralizing antibodies, while rSeV-GFP-P25 (group 3) induced negligible SRLV-specific antibody responses. Group 3 exhibited higher SRLV DNA copies in PBMCs but lower in most SRLV target tissues compared to control groups, with no SRLV DNA detected in spleen and bone marrow. Histomorphometry revealed reduced alveolar septal thickening in group 3, indicating partial protection against early SRLV-associated interstitial pneumonia. These results warrant further investigation into cellular immunity and long-term protection.

This study was funded by a grant from the Ministerio de Ciencia, Innovación y Universidades, Government of Spain under Grant RTI2018-096172-B-C33. Gobierno de Navarra (PC24-ECTIVAC-002-017-018). Álex Gómez is a PhD candidate funded by the Gobierno de Aragón [ORDEN CUS/803/2021]. We are grateful to Centro de Investigación Biomédica de Aragón (CIBA) for the assistance in the scanning of histopahological samples.