Immunogenicity, safety and dual DIVA-like character of a recombinant candidate vaccine against neosporosis in cattle

MENDOZA-MORALES, LUISA FERNANDA; FIORANI, FRANCO; MORÁN, KAREN DAIANA; HECKER, YANINA PAOLA; CIRONE, KARINA MARIELA; SÁNCHEZ-LÓPEZ, EDWIN FERNANDO; RAMOS-DUARTE, VICTOR ANDRÉS; CORIGLIANO, MARIANA GEORGINA; BILBAO, MARÍA GUILLERMINA; CLEMENTE, MARINA; MOORE, DADÍN PRANDO; SANDER, VALERIA ANALÍA

ACTA TROPICA

ELSEVIER SCIENCE BV

Año: 2024 vol. 257

0001-706X

Neosporosis is the major infectious cause of abortion and reproductive losses in cattle worldwide; however, thereare no available vaccines or drugs to control this disease. Recently, a dual (positive and negative) DIVA-like(Differentiation of Infected from Vaccinated Animals) vaccine was evaluated in a pregnant mouse model ofneosporosis, showing promising immunogenic and protective results. The current report aimed to study thesafety, the dose-dependent immunogenicity and the dual DIVA-like character of a recombinant subunit vaccinecomposed of the major surface antigen from Neospora caninum (rNcSAG1) and the carrier/adjuvant Heat shockprotein 81.2 from Arabidopsis thaliana (rAtHsp81.2) in cattle. Healthy heifers were separated and assigned toexperimental groups A-F and subcutaneously immunized with 2 doses of vaccine formulations 30 days apart asfollows: A (n = 4): 50 μg rNcSAG1 + 150 μg rAtHsp81.2; B (n = 4): 200 μg rNcSAG1 + 600 μg rAtHsp81.2; C (n =4): 500 μg rNcSAG1 + 1,500 μg rAtHsp81.2; D (n = 3): 150 μg rAtHsp81.2; E (n = 3):1,500 μg rAtHsp81.2, and F(n = 3) 2 ml of sterile PBS. The immunization of heifers with the different vaccine or adjuvant doses (groups A-E)was demonstrated to be safe and did not modify the mean value of the evaluated serum biomarkers of metabolicfunction (GOT/ASP, GPT/ALT, UREA, Glucose and total proteins). The kinetics and magnitude of the immuneresponses were dose-dependent. The higher dose of the vaccine formulation (group C) stimulated a broad andpotent humoral and cellular immune response, characterized by an IgG1/IgG2 isotype profile and IFN-γ secretion. In addition, this was the first time that dual DIVA-like character of a vaccine against neosporosis wasdemonstrated, allowing us to differentiate vaccinated from infected heifers by two different DIVA compliant testapproaches. These results encourage us to evaluate its protective efficacy in infected pregnant cattle in the future.