An Overview of Current Uses and Future Opportunities for Computer-Assisted Design of Vaccines for Neglected Tropical Diseases

Abstract

Neglected tropical diseases are infectious diseases that impose high morbidity and mortality rates over 1.5 billion people worldwide. Originally restricted to tropical and subtropical regions, changing climate conditions have increased their potential to emerge elsewhere. Control of their impact suffers from shortages like poor epidemiological surveillance or irregular drug distribution, and some NTDs still lack of appropriate diagnostics and/or efficient therapeutics. For these, availability of vaccines to prevent new infections, or the worsening of those already established, would mean a major breakthrough. However, only dengue and rabies count with approved vaccines at present. Herein, we review the state-of-the-art of vaccination strategies for NTDs, setting the focus on third generation vaccines and the concept of reverse vaccinology. Its capability to address pathogens´ biological complexity, likely contributing to save developmental costs is discussed. The use of computational tools is a fundamental aid to analyze increasingly large datasets aimed at designing vaccine candidates with the highest, possibly, opportunities to succeed. Ultimately, we identify and analyze those studies that took an in silico approach to find vaccine candidates, and experimentally assessed their immunogenicity and/or protection capabilities.

Keywords: epitopes; immunoinformatics; neglected tropical diseases; reverse vaccinology; vaccines.

Figure 1

(A) Search results for [NTD] or [pathogen] in question. (B) Search results for [NTD] or [pathogen] in question and [vaccine]. (C) Search results for [NTD] or [pathogen] in question and [epitope-based vaccine]. Blue bars represent NTDs, green bars pathogens, and red bars both. Numbers refer to: 1) Buruli ulcer; 2) Chagas disease; 3) Dengue; 4) Chikungunya; 5) Dracunculiasis; 6) Echinococcosis (Echinococcus granulosus); 7) Echinococcosis (Echinococcus multilocularis); 8) Food-borne trematodiases; 9) Human African trypanosomiasis; 10) Leishmaniasis; 11) Leprosy (Hansen´s disease); 12) Lymphatic filariasis (Wuchereria bancrofti); 13) Lymphatic filariasis (Brugia malayi); 14) Lymphatic filariasis (Brugia timori); 15) Mycetoma, chromoblastomycosis and other deep mycoses (fungi); 16) Mycetoma, chromoblastomycosis and other deep mycoses (bacteria); 17) Onchocerciasis; 18) Rabies (Rabies lyssavirus); 19) Rabies (Australian bat lyssavirus); 20) Scabies and other ectoparasites; 21) Schistosomiasis; 22) Soil transmitted helminthiases; 23) Snakebite; 24) Taeniasis/Cysticercosis; 25) Trachoma; and 26) Yaws.

Figure 2

Flowchart depicting the procedures followed to reach selected B-cell and T-cell epitopes. In each case, the legacy experimentation approach is indicated on the left.