Preclinical evaluation of a trivalent vaccine for treating/preventing candidal disease

Abstract Multiple-antigen vaccines are an increasing focus of biotherapeutic development targeting infectious disease. Three recombinant antigens, based on Candida albicans proteins, have independently induced protection in animal models of candidal infections; agglutinin-like sequence 3 (rAls3), hyphally regulated protein 1 (rHyr1), and secreted aspartyl proteinase 2 (rSap2). However, a trivalent vaccine with all 3 antigens has not been previously evaluated. Here we present murine immune data for monovalent and multivalent vaccine formulations, with and without aluminum hydroxide (AlOH). IgG titers are induced against each antigen in the trivalent vaccine, and all are higher with AlOH. Interference is seen with anti-rAls3 IgG titers when equal amounts of all 3 antigens are used. This interference is abrogated by decreasing rHyr1 and rSap2 amounts relative to rAls3. Dose-dependent IL-17A splenocyte responses were detected against rAls3 and rHyr1, but not rSap2, in monovalent formulations. With trivalent formulations, Als3- and Hyr1-specific IL-17A production increased additively in magnitude and numbers of mice responding and at lower doses compared to monovalent formulations. These data support that robust immune responses can be induced by all 3 antigens in a trivalent vaccine, which may improve efficacy for some or all disease indications by targeting multiple facets of the candidal pathogenesis pathway, including adhesion, invasion and dissemination.