Dual-antigen fusion protein vaccination induces protective immunity against <i>Candida albicans</i> infection in mice

<i>Candida albicans</i> Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of <i>C. albicans</i>, using AlPO₄ as an adjuvant. The AH vaccine was constructed by fusing Als3_17-432 and Hyr1_25-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO₄, followed by a lethal challenge with <i>C. albicans</i> SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO₄ combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (<i>p</i> < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (<i>p</i> < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (<i>p</i> < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (<i>p</i> < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO₄ vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in <i>C. albicans</i> infections. These findings support further development of dual-antigen vaccine strategies.