Design of a multi-epitope vaccine against the pathogenic fungi Candida tropicalis using an in silico approach

Nahid Akhtar; Arshwinder Singh; Atul Kumar Upadhyay; M Amin-Ul Mannan

doi:10.1186/s43141-022-00415-3

Design of a multi-epitope vaccine against the pathogenic fungi Candida tropicalis using an in silico approach

J Genet Eng Biotechnol. 2022 Sep 29;20(1):140. doi: 10.1186/s43141-022-00415-3.

Authors

Nahid Akhtar¹, Arshwinder Singh², Atul Kumar Upadhyay², M Amin-Ul Mannan^{3

4}

Affiliations

¹ Department of Molecular Biology and Genetic Engineering, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, 144401, Punjab, India.
² Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India.
³ Department of Molecular Biology and Genetic Engineering, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, 144401, Punjab, India. mannan.phd@gmail.com.
⁴ Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation at Harbor, University of California Los Angeles (UCLA) Medical Center, Los Angeles, CA, USA. mannan.phd@gmail.com.

Abstract

Background: Candida tropicalis causes tropical invasive fungal infections, with a high mortality. This fungus has been found to be resistant to antifungal classes such as azoles, echinocandins, and polyenes in several studies. As a result, it is vital to identify novel approaches to prevent and treat C. tropicalis infections. In this study, an in silico technique was utilized to deduce and evaluate a powerful multivalent epitope-based vaccine against C. tropicalis, which targets the secreted aspartic protease 2 (SAP2) protein. This protein is implicated in virulence and host invasion.

Results: By focusing on the Sap2 protein, 11 highly antigenic, non-allergic, non-toxic, and conserved epitopes were identified. These were subsequently paired with RS09 and flagellin adjuvants, as well as a pan HLA DR-binding epitope (PADRE) sequence to create a vaccine candidate that elicited both cell-mediated and humoral immune responses. It was projected that the vaccine design would be soluble, stable, antigenic, and non-allergic. Ramachandran plot analysis was applied to validate the vaccine construct's 3-dimensional model. The vaccine construct was tested (at 100 ns) using molecular docking and molecular dynamics simulations, which demonstrated that it can stably connect with MHC-I and Toll-like receptor molecules. Based on in silico studies, we have shown that the vaccine construct can be expressed in E. coli. We surmise that the vaccine design is unrelated to any human proteins, indicating that it is safe to use.

Conclusions: The vaccine design looks to be an effective option for preventing C. tropicalis infections, based on the outcomes of the studies. A fungal vaccine can be proposed as prophylactic medicine and could provide initial protection as sometimes diagnosis of infection could be challenging. However, more in vitro and in vivo research is needed to prove the efficacy and safety of the proposed vaccine design.

Keywords: Antifungals; Candidiasis; Computational biology; Epitope vaccine; Molecular simulation; Reverse vaccinology.

Grants and funding

EMR/2017/002299/Science and Engineering Research Board