In Silico Designing of a Multitope Vaccine against Rhizopus microsporus with Potential Activity against Other Mucormycosis Causing Fungi.

Mohamed A Soltan,Nada Elbassiouny,Dalia A El-Damasy,Hanaa Abd El-Gayyed,Ashraf E Sileem,Sameh S Elhady,Khaled M Darwish,Hasnaa L Kamel,Khalid Abd El Ghany,Eman Fayad,Ola A Abu Ali,Kareem M Abdelraheem,Mohammed F Sheha,Muhammad Alaa Eldeen,Ahmed M Gouda

doi:10.3390/cells10113014

Abstract

During the current era of the COVID-19 pandemic, the dissemination of Mucorales has been reported globally, with elevated rates of infection in India, and because of the high rate of mortality and morbidity, designing an effective vaccine against mucormycosis is a major health priority, especially for immunocompromised patients. In the current study, we studied shared Mucorales proteins, which have been reported as virulence factors, and after analysis of several virulent proteins for their antigenicity and subcellular localization, we selected spore coat (CotH) and serine protease (SP) proteins as the targets of epitope mapping. The current study proposes a vaccine constructed based on top-ranking cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes from filtered proteins. In addition to the selected epitopes, β-defensins adjuvant and PADRE peptide were included in the constructed vaccine to improve the stimulated immune response. Computational tools were used to estimate the physicochemical and immunological features of the proposed vaccine and validate its binding with TLR-2, where the output data of these assessments potentiate the probability of the constructed vaccine to stimulate a specific immune response against mucormycosis. Here, we demonstrate the approach of potential vaccine construction and assessment through computational tools, and to the best of our knowledge, this is the first study of a proposed vaccine against mucormycosis based on the immunoinformatics approach.

Highlights

Mucormycosis is an invasive fungal infection caused by a diverse group of fungi belonging to the order Mucorales [1]
The usage of in silico approaches in designing and validating vaccines computationally can save both time and cost. This can be explained by considering the microorganisms that are difficult to be cultivated or infections that are caused by a group of microorganisms, such as mucormycosis; computational tools can save time and analyze the proteome of these types of microorganisms and detect potential vaccine candidates
After investigation of the conservancy of every single epitope that constructs the current study’s multitope vaccine, in seven major mucormycosis-causing fungi, we found that at least two single epitopes were 100% conserved in each fungus, which recommends the current study’s multitope vaccine as a general vaccine against mucormycosis

Summary

Introduction

Mucormycosis is an invasive fungal infection caused by a diverse group of fungi belonging to the order Mucorales [1]. With the outbreak of COVID-19, many cases of mucormycosis have been reported in people infected with COVID-19 around the world and especially in India [7]. This correlation was attributed to the excellent environment of high glucose, low oxygen, and decreased fighting activity of white blood cells in patients infected with COVID-19, which made it easy for Mucorales spores to germinate [8]. Before the current time of the COVID-19 pandemic, which facilitates the spreading of mucormycosis, the United States health care system cost about $50 million per year for the management of mucormycosis cases, leading to the question about the economic value of developing a vaccine against mucormycosis, where analysis and studies proved the requirement of an effective vaccine that will reduce the infection rate and mortality in a cost-effective manner [11]

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Conclusion