Ayiseh, R. B. | bioRxiv Science

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↗

bioRxiv2025

Investigating the Role of Onchocerca ochengi in Epilepsy Development: A Gerbil Model Study

BackgroundOnchocerca volvulus infection is linked to onchocerciasis-associated epilepsy (OAE) in humans, but the role of Onchocerca ochengi in epilepsy development remains unexplored. This study aimed to investigate whether O. ochengi infection contributes to epilepsy development. Methodology/Principal FindingsGerbils were implanted with O. ochengi worm masses (test group) or underwent sham surgery (control group). Behavioral and physical assessments were performed between days 15-19 using multiple tests, including the elevated plus maze, open-field, object recognition, and hanging wire tests. On day 21, gerbils were sacrificed, and body/organ weights were recorded, along with worm mass survival. Implantation of 15 worm masses resulted in 100% mortality in the test group, while implantation of 10 worm masses resulted in 53.3% mortality, with all control animals surviving. At day 21, worm mass survival averaged 1.4 out of 10, with a viability score of 93.3%. Test animals showed significant reductions in body weight and increased spleen weight compared to controls, but no significant behavioral differences were observed. Conclusions/SignificanceWhile O. ochengi infection caused notable physical effects, including high mortality and changes in body/organ weights, no behavioral evidence of epilepsy was observed. The high mortality rate and limited observation period restrict the interpretation of these findings. Further studies with larger cohorts and longer observation periods are needed to assess the potential role of Onchocerca spp. in epilepsy development. To the best of our knowledge, this study represents the first attempt to establish an animal model for OAE. Author SummaryOnchocerca volvulus infection is linked to onchocerciasis-associated epilepsy (OAE) in humans, but we know less about whether other types of Onchocerca, such as Onchocerca ochengi, might also contribute to epilepsy. Our study aimed to investigate this question by infecting gerbils with O. ochengi worm masses and observing the impact on their behavior and physical health. We found that while the infection caused significant physical changes, including high mortality rates and changes in body and organ weights, there were no signs of behavioral changes typical of epilepsy. In particular, we did not see any of the usual neurological symptoms that might indicate epilepsy. These results suggest that while O. ochengi can affect animal health in some ways, it might not be directly involved in causing epilepsy. However, the high mortality rate in the infected gerbils and the relatively short duration of the study mean that we cannot draw firm conclusions. Future research with more animals and a longer time frame will be important to better understand whether Onchocerca worms contribute to epilepsy development in humans.

neuroscience↗