In Silico Design of Multi-Epitope ESAT-6:Ag85b:Fcγ2a Fusion Protein as a Novel Candidate for Tuberculosis Vaccine

Abstract

: Mycobacterium tuberculosis (MTB), which is the causative agent of tuberculosis (TB), is among the most important infectious bacteria with high morbidity and mortality rates worldwide. Bacilli Calmette-Guerin (BCG) vaccine has been discovered for about a century, and it is considered as a major vaccine for humans. However, some factors, such as its attenuated nature and its inefficacy against the latent form of the disease, have led to the use of alternative vaccines. Multi-epitope subunit vaccines are new-generation vaccines that are being developed in clinical trial phases. For the production of a subunit vaccine, the selection of immunodominant antigens and targeted delivery systems to antigen presenting cells (APCs) are considered as basic parameters. In the present study, we designed the novel multi-epitope ESAT-6:Ag85B:Fcγ2a, which was evaluated completely by various online tools as an optimum vaccine against TB. The early secreted antigenic target of 6 kDa (ESAT-6) and antigen 85B (Ag85B) are two immunodominant antigens, and Fcγ2a is a targeted delivery system. This vaccine candidate can be used for future preclinical studies.

Beijing genotype of Mycobacterium tuberculosis is associated with extensively drug-resistant tuberculosis: A global analysis

“…According to the WHO, there were about 10 million people who fell ill with TB in 2019; Furthermore, there were 1.5 million TB deaths in 2019 [ 3 ]. Despite more than a century of extensive studies, the control and eradication of tuberculosis have yet remained a global challenge and one of the medical emergencies considered by the World Health Organization [ 4 , 5 ].…”

A Structural View at Vaccine Development against M. tuberculosis

“…Structure-based epitope mapping of the Mtb secterory antigen MTC28 allowed the identification of its immunogenic part, by coupling X-ray crystallography with experimental and computational epitope mapping [112]. Computational tools were also used for the design of a multi-epitope using ESAT-6 and Ag85B as two main secretory antigens in the active Phase of Mtb infection, and Fcγ2a as targeted delivery system [113]. Furthermore, an integrated computational approach was used to design a multi-epitope vaccine based on two antigenic proteins, diacylglycerol acyltransferase and ESAT-6-like protein [114].…”

Review on Bovine Tuberculosis: An Emerging Disease Associated with Multidrug-Resistant Mycobacterium Species

“…The study helped to estimate pulmonary TB prognosis and provided a probe into targeted molecular treatment. Keikha et al in Iran used in silico tools for designing a multi-epitope ESAT-6: Ag85b: Fcγ2a fusion protein as a novel candidate for a TB vaccine [ 133 ]. More recently, Bibi et al in China applied advanced computational techniques to develop a universal TB vaccine [ 134 ].…”