Nchanji, G. T. | bioRxiv Science

bioRxiv2025

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

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).

immunology↗

bioRxiv2024

Predictive Immunoinformatics Reveal Promising Safety and Anti-Onchocerciasis Protective Immune Response Profiles to Vaccine Candidates (Ov-RAL-2 and Ov-103) in Anticipation of Phase I Clinical Trials

Onchocerciasis is a devastating tropical disease that causes severe eye and skin lesions. As global efforts shift from disease control to elimination, prophylactic/therapeutic vaccines have emerged as alternative elimination tools. Notably, Ov-RAL-2 and Ov-103 antigens have shown great promise in preclinical studies and plans are underway for clinical trials. Here, we predict the immunogenicity and other vaccine-related parameters for both antigens using immunoinformatics, as potential vaccine candidates against onchocerciasis. The analysis reveals that both antigens exhibit a favourable safety profile, making them promising candidates poised for human trials. Importantly, in silico immune simulation forecasts heightened antibody production and sustained cellular responses for both vaccine candidates. Indeed, the antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes associated with protective responses against onchocerciasis, as well as the potential for stimulating innate immune TLR-4 receptor recognition with Ov-103 exhibiting better structural efficiency and antigenicity with no homology to human proteins compared to Ov-RAL-2. Overall, we provide herein valuable insights for advancing the development of Ov-103 and RAL-2 vaccine candidates against onchocerciasis in humans. Authors summaryTo address the significant impact of onchocerciasis, a tropical disease commonly known as river blindness, we have employed computational tools to assess the viability of two promising vaccine candidates, namely Ov-RAL-2 and Ov-103. Existing control strategies alone are insufficient to eliminate the disease. Our study utilises advanced immunoinformatics techniques to systematically evaluate the safety, antigenicity, and immunogenic properties of these antigens as potential vaccine candidates against onchocerciasis prior to human trials. Our analysis revealed that both vaccine candidates demonstrate favourable safety profiles and possess the capability to induce robust antibody responses and cellular immunity. Notably, we identified numerous distinct epitopes present within each vaccine candidate that are associated with protective immunity against onchocerciasis. The abundance of these epitopes suggests that both vaccine candidates have the potential to activate the immune system through diverse humoral and cellular response mechanisms. By providing these valuable insights, our research assists in guiding the development of Ov-103 and Ov-RAL-2 as effective vaccines against onchocerciasis. Ultimately, our findings contribute to the global endeavour to eliminate this debilitating disease and enhance the quality of life for the millions of affected individuals.

bioinformatics↗