One Health Approach to the Computational Design of a Lipoprotein-Based Multi-Epitope Vaccine Against Human and...

Tuberculosis (TB) remains a major cause of ill health and one of the leading causes of death worldwide, with about 1.25 million deaths estimated in 2023. Control measures have focused principally on early diagnosis, the treatment of active TB, and vaccination. However, the widespread emergence of anti-tuberculosis drug resistance remains the major public health threat to progress made in global TB care and control. Moreover, the Bacillus Calmette-Guérin (BCG) vaccine, the only licensed vaccine against TB in children, has been in use for over a century, and there have been considerable debates concerning its effectiveness in TB control. A multi-epitope vaccine against TB would be an invaluable tool to attain the Global Plan to End TB 2023-2030 target. A rational approach that combines several B-cell and T-cell epitopes from key lipoproteins was adopted to design a novel multi-epitope vaccine candidate. In addition, interactions with TLR4 were implemented to assess its ability to elicit an innate immune response. The conservation of the selected proteins suggests the possibility of cross-protection in line with the One Health approach to disease control. The vaccine candidate was predicted to be both antigenic and immunogenic, and immune simulation analyses demonstrated its ability to elicit both humoral and cellular immune responses. Protein-protein docking and normal-mode analyses of the vaccine candidate with TLR4 predicted efficient binding and stable interaction. This study provides a promising One Health approach for the design of multi-epitope vaccines against human and livestock tuberculosis. Overall, the designed vaccine candidate demonstrated immunogenicity and safety features that warrant further experimental validation in vitro and in vivo.