Biology subjects

Ghogomu, S. M.

Publications and source records attributed to Ghogomu, S. M..

4 recordsLinked to original sources

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↗

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↗

bioRxiv2024

Two highly selected mutations in the tandemly duplicated CYP6P4a and CYP6P4b drive pyrethroid resistance in Anopheles funestus

Gaining a comprehensive understanding of the genetic mechanisms underlying insecticide resistance in malaria vectors is crucial for optimising the effectiveness of insecticide-based vector control methods and developing diagnostic tools for resistance management. Considering the heterogeneity of metabolic resistance in major malaria vectors, the implementation of tailored resistance management strategies is essential for successful vector control. In this study, we provide evidence demonstrating that two highly selected mutations in the tandemly duplicated cytochrome P450 genes namely CYP6P4a and CYP6P4b, are driving pyrethroid insecticide resistance in the major malaria vector Anopheles funestus, in West Africa. Through a continent-wide polymorphism survey, we observed heightened indications of directional selection in both genes between 2014 and 2021. By conducting in vitro insecticide metabolism assays with recombinant enzymes expressed from both genes, we established that mutant alleles under selection exhibit higher metabolic efficiency compared to their wild-type counterparts. Furthermore, using the GAL4-UAS transgenic system, we demonstrated that transgenic Drosophila melanogaster flies overexpressing mutant alleles displayed an increased resistance to pyrethroids. These findings were in agreement with in silico characterisation, which highlighted changes in enzyme active site architecture that enhance the affinity of mutant alleles for type I and II pyrethroids. Furthermore, we developed two DNA-based assays capable of detecting the CYP6P4a-M220I and CYP6P4b-D284E mutations, showing their current confinement to West Africa. Genotype/phenotype correlation analyses revealed that these markers are strongly associated with resistance to types I and II pyrethroids and combine to drastically reduce the efficacy of pyrethroid bednets. Overall, our study makes available two field-applicable insecticide resistance molecular markers that will help in the monitoring and better management of insecticide resistance in West Africa. TeaserTwo field-applicable diagnostic tools for detecting metabolic resistance in Anopheles funestus to enhance insecticide resistance management in West Africa.

genetics↗