In silico design and computational characterization of novel chimeric multiepitope antigens for Mpox serosurveillance

Abstract

BackgroundThe Monkeypox (Mpox) virus is a zoonotic Orthopoxvirus with a global outbreak that began in 2022 and spread to more than 128 countries, with more than 132,000 confirmed cases and 1500 deaths. The pandemic preparedness pipeline emphasizes the importance of diagnostic surveillance of pathogens in at-risk populations to monitor transmission and mitigate the impact on public health. Unfortunately, the current gold standard diagnostic tool for Mpox is limited in its field applicability. Therefore, there is a crucial need for the development of robust novel diagnostic tools to enable continuous surveillance of the disease. As such, this work sought to design and validate novel multiepitope antigens as diagnostic tools for Mpox serosurveillance. MethodsUsing immunoinformatic approaches, two novel Mpox multiepitope antigens (MP-MEDA-1 and MP-MEDA-2) were designed using linear B-epitopes of viral proteins previously characterized in Mpox serodiagnosis. The 3D structures of the designed antigens were predicted, refined, and validated. Protein-protein docking and interaction analyses were performed between the designed diagnostic antigens and the Fab regions of human IgA, IgG, and IgM. ResultsThe designed antigens were predicted to be antigenic and demonstrated thermostability with desirable physicochemical properties. In addition, both antigens also demonstrated stable interactions with the Fab regions of selected immunoglobulins, with several residues interacting at the interfaces of all the docked complexes. ConclusionsThese preliminary findings highlight the potential of the MP-MEDA-1 and MP-MEDA-2 antigens as candidates to be further characterized for Mpox serosurveillance. The next phase of this project will focus on the expression and serological characterization of both antigens to determine their diagnostic parameters (sensitivity, specificity, and others).