In silico Design of a Multivalent Vaccine Against Candida albicans

Shikha Tarang,Laramie Lindgren,Sonia M Rocha-Sanchez,Blake Latendresse,Varun Kesherwani,Michael D Weston

doi:10.1038/s41598-020-57906-x

Shikha Tarang, Laramie Lindgren + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-57906-x

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Abstract

Invasive candidiasis (IC) is the most common nosocomial infection and a leading cause of mycoses-related deaths. High-systemic toxicity and emergence of antifungal-resistant species warrant the development of newer preventive approaches against IC. Here, we have adopted an immunotherapeutic peptide vaccine-based approach, to enhance the body’s immune response against invasive candida infections. Using computational tools, we screened the entire candida proteome (6030 proteins) and identified the most immunodominant HLA class I, HLA class II and B- cell epitopes. By further immunoinformatic analyses for enhanced vaccine efficacy, we selected the 18- most promising epitopes, which were joined together using molecular linkers to create a multivalent recombinant protein against Candida albicans (mvPC). To increase mvPC’s immunogenicity, we added a synthetic adjuvant (RS09) to the mvPC design. The selected mvPC epitopes are homologous against all currently available annotated reference sequences of 22 C. albicans strains, thus offering a higher coverage and greater protective response. A major advantage of the current vaccine approach is mvPC’s multivalent nature (recognizing multiple-epitopes), which is likely to provide enhanced protection against complex candida antigens. Here, we describe the computational analyses leading to mvPC design.

Highlights

Invasive candidiasis (IC) is one of the most common public health problems and is a major therapeutic challenge[1]
It consists of a truncated recombinant secreted aspartic protease 2 (Sap2), currently in clinical testing by Pevion BiotechAG10
While most vaccines focused only on one antigen, our approach involves the simultaneous targeting of multiple candida antigens which are molecularly linked to form a single recombinant protein

Summary

Introduction

Invasive candidiasis (IC) is one of the most common public health problems and is a major therapeutic challenge[1]. PEV7 is a virosomal vaccine to protect women suffering from chronic vaginal yeast infections (vulvovaginal candidiasis or VVC) It consists of a truncated recombinant secreted aspartic protease 2 (Sap2), currently in clinical testing by Pevion BiotechAG10. NDV3 targets the recombinant N-terminal region of the hyphal protein agglutinin-like sequence three protein (rAls3p-N) and is being developed by NovaDigm Therapeutics[12] Another vaccination approach from Novartis Pharmaceuticals (Efungumab) based on monoclonal antibody targeting the heat shock protein 90 (Hsp90) progressed through to a Phase III clinical trial but was abandoned in later stages of development due to safety concerns[13]. Due to the complex nature of candida antigens and its ability to escape host-immune surveillance, a multi-epitope vaccine will likely be more beneficial in inducing a stronger and broader immune responses[15,16]. The findings presented in the current study detail in silico epitope mapping and provide future directions for vaccine design against C. albicans

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