Abstract
As part of GalvMed’s ‘Brucellosis Vaccine Prize’ initiative, our lab took on the challenge to develop a new vaccine for the control of small ruminant brucellosis that is superior to the one that has existed for more than 50 years. Based on our previous knowledge and experience in the development of vaccines for bovine and porcine brucellosis, we developed the vaccine strain B. melitensis Delta-pgm (BM Delta-pgm) by “clean” deletion of the phosphoglucomutase (pgm) coding gene. BM Delta-pgm has a general defect in sugar metabolism that prevents it from polymerizing polysaccharides containing glucose and/or galactose; therefore, it is unable to synthesize cyclic-beta-glucans and assemble the O-polysaccharide (O-PS) to the lipid A- core and, as a consequence, has a “rough” phenotype. These characteristics make BM Delta-pgm avirulent as we demonstrated extensively in the murine infection model. Immunological and vaccination/challenge studiesin the murine model indicate that BM Delta-pgm is immunogenic, generates a good IFN-gamma-mediated Th1 response, does not generate antibodies against O-PS and provides protection against challenge, not only by B. melitensis, but also by B. abortus and B. suis. These characteristics prompted us to evaluate the safety and protective efficacy of BM Delta-pgm in sheep. Between 2018 and 2019, we conducted four safety evaluations in ewes at early and late gestation. Abortigenicity, colonization and dissemination of the vaccine strain in milk and vaginal secretions were evaluated. The results indicate that BM Delta-pgm is safe and generates less than 4% abortions when applied to pregnant ewes. During 2020, an evaluation of the protective efficacy of the vaccine was performed in comparison with a non-vaccinated and a Rev.1 vaccinated control groups, all challenged with B. melitensis 16M at mid-gestation. Humoral and cellular immune response, lambing status, milk shedding, postpartum vaginal discharge and colonization of dams and lambs were evaluated. All parameters evaluated indicate that BM Delta-pgm is a safe vaccine strain, prevents abortion and colonization of dams and lambs conferring more than 90% protection against challenge with virulent strains. We propose BM Delta-pgm as a new vaccine with superior characteristics to the existing one for the control of brucellosis in small ruminants.
