Enhanced efficacy of recombinant Brucella abortus RB51 vaccines against B. melitensis infection in mice.
Brucella abortus strain RB51 is an attenuated rough strain, currently being used as the official live vaccine for bovine brucellosis in the USA and several other countries. In strain RB51, the wboA gene, encoding a glycosyltransferase required for the O-side chain synthesis, is disrupted by an IS711 element. Recently, we have demonstrated that strain RB51WboA, RB51 complemented with a functional wboA gene, remains rough but expresses low quantities of O-side chain in the cytoplasm. Mice vaccinated with strain RB51WboA develop greatly enhanced resistance against challenge with B. abortus virulent strain 2308. We have also demonstrated that overexpression of Cu/Zn superoxide dismutase (SOD) in strain RB51 (RB51SOD) significantly increases its vaccine efficacy against strain 2308 challenge. In this study, we constructed a new recombinant strain, RB51SOD/WboA, that over expresses SOD with simultaneous expression of O-side chain in the cytoplasm. We tested the vaccine potential of strains RB51SOD, RB51WboA, RB51SOD/WboA against challenge with virulent Brucella melitensis 16M and B. abortus 2308 in mice. In comparison with strain RB51, strain RB51SOD induced better protection against strain 2308, but not strain 16M, challenge. Similar to strain RB51WboA, vaccination with strain RB51SOD/WboA resulted in complete protection of the mice from infection with strain 2308. When challenged with strain 16M, mice vaccinated with either strain RB51WboA or strain RB51SOD/WboA were significantly better protected than those vaccinated with strain RB51 or RB51SOD. These results suggest that strains RB51WboA and RB51SOD/WboA are good vaccine candidates for inducing enhanced protection against B. melitensis infection.
Department of Veterinary Pathobiology, School of Veterinary Medicine, Purdue University, 725 Harrison Street, West Lafayette, IN 47907, USA. rvemulap@purdue.edu
Ramesh
R
Vemulapalli
Andrea
A
Contreras
Neelima
N
Sanakkayala
Nammalwar
N
Sriranganathan
Stephen M
SM
Boyle
Gerhardt G
GG
Schurig
D000818:Animals; D001428:Bacterial Vaccines; D002004:Brucella Vaccine / Q000235:genetics / Q000276:immunology*; D002003:Brucella abortus / Q000235:genetics / Q000276:immunology*; D017347:Brucella melitensis / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D002006:Brucellosis / Q000382:microbiology / Q000517:prevention & control / Q000662:veterinary*; D002417:Cattle; D005798:Genes, Bacterial; D016695:Glycosyltransferases / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D019081:O Antigens / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012698:Serologic Tests / Q000662:veterinary; D013482:Superoxide Dismutase / Q000235:genetics; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
D001428:Bacterial Vaccines; D002004:Brucella Vaccine; D019081:O Antigens; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D013482:Superoxide Dismutase; D016695:Glycosyltransferases