Safety, Tolerability, and Immunogenicity of a Recombinant, Genetically Engineered, Live-Attenuated Vaccine against Canine Blastomycosis

Abstract

Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 ؋ 10 4 to 2 ؋ 10 7 yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of <2 ؋

Evaluation of the Therapeutic Effect of Radioattenuated Yeast Cells in Experimental Paracoccidioidomycosis

“…A recombinant attenuated strain of Blatomyces dermatitidis has been promising as a potential vaccine against blastomycosis experimental [34,35]. Currently, the safety, tolerability and immunogenicity of this live-attenuated vaccine have been tested in dogs [36].…”

Blastomycosis

“…Intradermal administration of an attenuated B. dermatitidis lacking BAD-1 protects mice against lethal pulmonary challenge but intranasal vaccine delivery fails to do so [37]. Mucosal vaccination leads to poor T cell activation by induction of matrix metalloproteinase two, which impairs the chemokine response [35]. These studies in mice [37] and dogs [35] are promising and indicate that the development of a vaccine to prevent disease in humans is possible.…”

“…Mucosal vaccination leads to poor T cell activation by induction of matrix metalloproteinase two, which impairs the chemokine response [35]. These studies in mice [37] and dogs [35] are promising and indicate that the development of a vaccine to prevent disease in humans is possible.…”

“…The protein contains a repetitive domain that mimics thrombospondin type-1 (TSP-1) and suppresses T lymphocyte activation and effector function by binding heparin sulfate [34]. BAD-1 is a major virulence factor and its deletion results in attenuated pathogenicity [35,36]. Cellular immunity in humans, as determined by antigeninduced lymphocyte proliferation, has been documented using whole yeast phase organisms, an alkali-soluble, water-soluble yeast extract, and BAD-1 [3,4].…”

Fungal cell wall vaccines: an update

“…This antigen has been protective in mice, probably mainly through a Th2-type response. Recently, the group has used the innovative strategy of a live, attenuated vaccine in beagles and foxhounds (Wüthrich et al , 2011a). BAD-1 is a cell surface protein, which is an adhesion for B. dermatitidis (Brandhorst et al , 1999).…”