Immunoinformatic design of a putative multi-epitope vaccine candidate against Trypanosoma brucei gambiense

Human African trypanosomiasis (HAT) is a neglected tropical disease that is caused by flagellated parasites of the genus Trypanosoma. HAT imposes a significant socio-economic burden on many countries in sub-Saharan Africa and its control is hampered by several drawbacks ranging from the ineffectiveness of drugs, complex dosing regimens, drug resistance, and lack of a vaccine. Despite more than a century of research and investigations, the development of a vaccine to tackle HAT is still challenging due to the complex biology of the pathogens. Advancements in computa-tional modeling coupled with the availability of an unprecedented amount of omics data from dif-ferent organisms have allowed the design of new generation vaccines that offer better antigenicity and safety profile. One of such new generation approaches is a multi-epitope vaccine (MEV) designed from a collection of antigenic peptides. A MEV can stimulate both cellular and humoral immune responses as well as avoiding possible allergenic reactions. Herein, we take advantage of this approach to design a MEV from conserved hypothetical plasma membrane proteins of Trypanosoma brucei gambiense, the trypanosome subspecies that is responsible for the west and cen-tral African forms of HAT. The designed MEV is 402 amino acids long (41.5 kDa). It is predicted to be antigenic, non-toxic, to assume a stable 3D conformation, and to interact with a key immune receptor. In addition, immune simulation foresaw adequate immune stimulation by the putative antigen and a lasting memory. Therefore, the designed chimeric vaccine represents a potential can-didate that could be used to target HAT.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Automated summary

Human African trypanosomiasis (HAT) is a neglected tropical disease caused by flagellated parasites. It imposes a significant socio-economic burden on sub-Saharan African countries, and its control is hindered by drug ineffectiveness, complex dosing regimens, drug resistance, and lack of a vaccine. Researchers have utilized computational modeling and omics data to design a multi-epitope vaccine (MEV) composed of antigenic peptides, which offers improved antigenicity and safety. The designed MEV could serve as a potential candidate for targeting HAT.