In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases

Abstract

Onchocerciasis is a parasitic disease with high socio-economic burden particularly in sub-Saharan Africa. The elimination plan for this disease has faced numerous challenges. A multi-epitope prophylactic/therapeutic vaccine targeting the infective L3 and microfilaria stages of the parasite’s life cycle would be invaluable to achieve the current elimination goal. There are several observations that make the possibility of developing a vaccine against this disease likely. For example, despite being exposed to high transmission rates of infection, 1 to 5% of people have no clinical manifestations of the disease and are thus considered as putatively immune individuals. An immuno-informatics approach was applied to design a filarial multi-epitope subunit vaccine peptide consisting of linear B-cell and T-cell epitopes of proteins reported to be potential novel vaccine candidates. Conservation of the selected proteins and predicted epitopes in other parasitic nematode species suggests that the generated chimera could be helpful for cross-protection. The 3D structure was predicted, refined, and validated using bioinformatics tools. Protein-protein docking of the chimeric vaccine peptide with the TLR4 protein predicted efficient binding. Immune simulation predicted significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2. Overall, the constructed recombinant putative peptide demonstrated antigenicity superior to current vaccine candidates.

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans – An Integrated Vaccinomics Approach

“…Satisfactorily, the obtained CAI value (0.986) was very close to 1.0 and GC contents (56.60%) was also within the optimal limit (30-70%) indicating possible higher expression within E. coli K12 system (Shey et al 2019;Morla, Makhija, and Kumar 2016). As a suggestion for prospective vaccine synthesis, in silico cloning was also performed using pET30a(+) vector.…”

“…The vaccine construct has 520 amino acid residues including an adjuvant LprG which alone constitutes 241 residues. Chatterjee and coworkers have designed a multi-epitope vaccine which was 568 amino acid long (Chatterjee et al 2018 (Shey et al 2019;Rahmani et al 2019;Khatoon, Pandey, and Prajapati 2017). Moreover, the linkers were added to facilitate the functional preservation of each epitope (⁓9-15 residues) so that they can function separately after being imported into the human body (Pandey, Bhatt, and Prajapati 2018).…”

“…Besides, S-tag sequence increases protein stability by providing its abundance of charged and polar residues (Raines et al 2000). Moreover, in silico cloning with pET30a(+) vector was described earlier (Shey et al 2019).…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…The vaccines are made from short peptide fragments capable of eliciting highly specific immune responses, precision targeting and multiepitope constructs, in the case of varying antigenic peptides, which has been made feasible with the advancements in the field of computational biology. [113][114][115][116] Vaccines for pathogens with immune escape potentials can basically be constructed by using most, if not all, of their immunogenic peptides 116,117 because such vaccines prove to be better than single-epitope and classical vaccines. Multiepitope vaccines enjoy the following advantages over single-epitope and classical vaccines: a) they are an assemblage of several epitopes obtained from distinct protein targets/antigens of an intended infection; b) the multiple T-cell receptors (TCRs) in the vaccine recipient can easily recognize vaccines with multiple HLA epitopes; c); they can be easily adjuvanted to improve their immunogenicity; d) they can activate antibody-mediated and cell-mediated immunological responses because of their overlapping helper T lymphocytes (HTL), CD8+ T-cell and B-cell epitopes; and e) unwanted protein antigens are excluded in such construct thereby reducing the chances of untoward effects and/ or immune responses likely to cause disease(s).…”

Immunoinformatic and dynamic simulation-based designing of a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis

“…Designing of multiepitope vaccine construct. The multiepitope vaccine construct was designed by combining adjuvant, CTL, HTL and LBL epitopes with appropriate linkers as reported earlier 27,36 . An adjuvant is an immunogenic composition that may boost the specific and long-lasting immune response against an antigen by a variety of mechanisms 68 .…”