Immunoinformatics Approach to Design a Novel Subunit Vaccine Against Visceral Leishmaniasis

Abstract

Visceral leishmaniasis (VL) infection is mostly caused by Leishmania donovani and affects countries worldwide. Despite the need for a safe and effective vaccine against leishmaniasis due to the increased drug resistance, however, no vaccine has yet been licensed for clinical use. This study revolves around the immunoinformatics approach to design a multi-epitope vaccine against VL infection. In this case, the proteome of L. donovani has been investigated, and three host non-homologous and antigenic extracellular secretory proteins have been identified as potential vaccine candidates with low transmembrane helices (≤ 1). The multi-epitope subunit vaccine construct consists of T-cell (cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL)) epitopes accompanied by appropriate adjuvant and linkers. A 372-amino acid vaccine construct has been established with specific characteristics, such as soluble, stable, antigenic, non-allergenic, non-toxic, and non-host homologous. Besides, the tertiary structure of the designed vaccine was modeled and validated. Also, the stability and affinity of the vaccine- TLR4 complex were confirmed by using molecular docking and molecular dynamics (MD) simulation. In addition, in silico immunization assay showed the efficiency of this candidate vaccine to stimulate an effective immune response. Furthermore, the refined vaccine was optimized and cloned in the pET28a (+) vector, and its successful expression was confirmed virtually. However, the experimental validation is required to verify the multi-epitope vaccine efficacy against VL infection.

Development of a multi-epitope vaccine candidate for leishmanial parasites applying immunoinformatics and in vitro approaches

“…The residues of the epitopic region elucidate distinct secondary structural elements possessing α-helices predominantly. A three-dimensional structure of vaccine protein was generated and that presented better quality than the ones obtained from previously designed multi-epitope leishmanial vaccines ( 45 , 54 , 55 ). As the conformational stability of folded proteins depends upon several interactions, including disulfide bonds ( 56 ), disulfide-engineered vaccine protein showed more physiochemical and structural stability that was further evidenced by molecular dynamics simulation.…”

“…As the multi-epitope vaccines are designed to enhance the summative effect of cellular, humoral, and innate immune responses, they possess an edge over the monovalent candidates/formulations (41). Recently, several attempts have been made to employ the immunoinformatics approach for designing and assessing multi-epitope vaccine constructs for leishmanial parasites (42)(43)(44)(45)(46). In this study, a new multi-epitope vaccine candidate has been proposed from LdMAcP that plays a substantial role in parasitic virulence.…”

Multiepitope‐based vaccine design by exploring antigenic potential among leptospiral lipoproteins using comprehensive immunoinformatics and structure‐based approaches

“…A multiepitope vaccine combined with novel adjuvants such as Toll‐like receptor (TLR), TLR2 or TLR4 agonists proved relatively immunogenic and successful in vaccine design. This approach has successfully been applied and is also being used extensively against various infectious diseases such as malaria, leishmaniosis, and COVID‐19 24–26 …”

“…This approach has successfully been applied and is also being used extensively against various infectious diseases such as malaria, leishmaniosis, and COVID-19. [24][25][26] In this study, using available bioinformatics tools, we evaluated the antigenicity of LipL proteins from Leptospira and designed a multiepitope chimeric vaccine. The chimeric vaccine construct was then validated by predicting its secondary structure contents, tertiary structure, and other physicochemical properties.…”