Recombinant PsoSP4 confers superior 80% protection against psoroptic mange in rabbits in association with a Th1-biased immune response.

Psoroptic mange, caused by Psoroptes ovis, is a severe global ectoparasitic disease for which no commercial vaccine is available. Here, we evaluated four recombinant P. ovis proteins (rPsoSP4, rPsoPRF, rPsoMIF, and rPsoSP5) as subunit vaccine candidates in a rabbit model. Three antigens conferred significant and graded protection, with final protection rates of 80% (rPsoSP4), 60% (rPsoPRF) and 20% (rPsoMIF), compared to 0% in the control and rPsoSP5-vaccinated groups. The lead candidate, rPsoSP4, reduced ear lesion scores, crust weights, and mite burden by up to 88.57%, 88.30%, and 81.80%, respectively. To our knowledge, rPsoSP4 is the most efficacious defined antigen against psoroptic mange reported to date, outperforming the previously tested single recombinant antigen and even a seven-protein cocktail vaccine. Mechanistically, protection correlated with a balanced, Th1-skewed immune signature. The high-level protection conferred by rPsoSP4 was characterized by elevated IFN-γ coupled with restrained Th-17A levels. In contrast, the non-protective rPsoSP5 vaccine elicited a singularly skewed Th17 response. Furthermore, antigen-specific IgG levels did not always correlate positively with protection (rPsoSP5), but a moderate yet significant elevation in total IgE was observed in the protected groups (rPsoPRF, rPsoMIF). This suggests a potential contributory role for IgE-mediated effector mechanisms in the anti-mite response. Our results identify rPsoSP4 as a highly efficacious single-antigen vaccine candidate and validate rPsoPRF and rPsoMIF as viable alternatives.