Shintouo, C. M. | Search bioRxiv

bioRxiv2025

Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, OvMANE1: preclinical evaluation in mice model

Onchocerciasis, caused by the filarial worm Onchocerca volvulus, remains a major public health challenge due to the limitations of ivermectin-based control strategies, thereby, highlighting the need for more innovative tools like vaccines. This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, OvMANE1 formulated with Freunds adjuvant, in BALB/c mice. Following mice immunization at three time points of 2-week intervals, adjuvanted-OvMANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG levels after the first (p = 0.0260) and final booster doses (p = 0.026). Interestingly, total IgG (p = 0.0086) and IgG1 (p = 0.0465) levels also increased significantly over the study period highlighting the ability of OvMANE1 to sustain humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leukocyte count (p = 0.0190) and increased lymphocyte activity (p = 0.0397) observed in the adjuvanted-OvMANE1 group compared to the control. Indeed, total leukocytes increased progressively from day 0 to day 39, with significant differences recorded in the test group between doses: day 0 vs. day 14 (p = 0.0043) and day 14 vs. day 28 (p = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity strongly suggests that the antigen can elicit mixed Th1/Th2 responses and antibody-dependent cellular cytotoxicity (ADCC) targeting O. volvulus L3 and/or other larval stages of the parasite. These results clearly show the emergence of OvMANE1 as a promising vaccine candidate against human onchocerciasis. However, further studies to evaluate the antigens protective potential in other animal species are required.

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↗