P481 Antifungal vaccines: An alternative approach to combat multidrug resistance in the post-antibiotic era

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMAlexander Fleming's discovery of the antibiotic ‘Penicillin’ and many more has inspired after saving millions of lives and spared immeasurable suffering worldwide. However, he also warned about the consequences of abuse of antibiotics that could lead to the expiry of the golden age of antibiotics. Current decreasing effectiveness of antibiotics in general and antifungals in particular, evolution of new drug-resistant forms, and species and lack of commercial interests to develop new antifungals is a clear indication of a post-antibiotic era. There is an amplified warning for the pharmaceutical industries, academic and research institutions, and governments to invest the necessary resources to produce next-generation, safe and effective antifungal vaccines. Candida auris is one of the emerging pan-resistant pathogenic yeast among immunocompromised patients worldwide. Early diagnostics and vaccines are the best alternatives to handle this drug-resistant pathogen. Cell wall proteins are responsible for eliciting an immune response in the host and therefore, can be promising candidates for the development of therapeutic biomarkers and vaccines against C. auris.Antifungal susceptibility profiling against standard antifungal drugs was performed using CLSI guidelines. The cell wall proteome was characterized by using LC-MS followed by bioinformatic and functional analyses. Furthermore, the protective effect of the cell wall-associated protein against C. auris infection was evaluated in BALB/c female mice.A total of 60 proteins were predicted to be immunodominant. In vivo results demonstrated lowered fungal burden in target organs and increased survival in vaccinated mice as compared with the infection control group revealing the immunogenic property of cell wall-associated proteins.This study validates the mass-spectrometry approach to identify antigenic proteins of C. auris and the potential of these proteins to serve as biomarkers for the development of diagnostic assays and/or vaccines against infections caused by C. auris.