Next-generation Candida albicans vaccine VXV-01 containing recombinant Als3p and Hyr1p antigens for invasive Candida infections.

Candida species, including Candida albicans and Candida auris, represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. C. albicans is known for causing both superficial and invasive infections, while C. auris is a newly emerged, multidrug-resistant pathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstream infections. Vaccine candidates targeting C. albicans hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protected against recurrent vulvovaginal candidiasis in women. We earlier showed that both Als3p and Hyr1p have orthologs in C. auris, and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protected mice from multidrug resistant C. auris candidemia. Here, we optimized VXV-01, an Als3p and Hyr1p dual antigen vaccine formulated with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T cell-dependent protection against lethal C. albicans and C. auris. The VXV-01 vaccine did not antagonize antifungal drug therapy and showed higher overall mouse survival than mice receiving the vaccine or antifungal drug alone, albeit this difference did not reach statistical significance. This study highlights the potential of VXV-01 in providing durable protective immunity against hematogenously disseminated C. albicans and C. auris and mucosal C. albicans infections.