{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:45:41Z","timestamp":1789962341018,"version":"4.0.1"},"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025. Notably,\n                    <jats:italic>Ov<\/jats:italic>\n                    -RAL-2 and\n                    <jats:italic>Ov<\/jats:italic>\n                    -103 antigens have shown great promise during pre-clinical development, however, the overall success rate of vaccine candidates during clinical development remains relatively low due to certain adverse effects and immunogenic limitations. This study, thus, aimed at predicting the safety and immunogenicity of\n                    <jats:italic>Ov<\/jats:italic>\n                    -RAL-2 and\n                    <jats:italic>Ov<\/jats:italic>\n                    -103 potential onchocerciasis vaccine candidates prior to clinical trials. Advanced molecular simulation models and analytical immunoinformatics algorithms were applied to predict potential adverse side effects and efficacy of these antigens in humans. The analyses revealed that both\n                    <jats:italic>Ov<\/jats:italic>\n                    -RAL-2 and\n                    <jats:italic>Ov<\/jats:italic>\n                    -103 demonstrate favourable safety profiles as toxicogenic and allergenic epitopes were found to be absent within each antigen. Also, both antigens were predicted to harbour substantial numbers of a wide range of distinct epitopes (antibodies, cytokines, and T- Cell epitopes) associated with protective immunity against onchocerciasis. In agreement, virtual vaccination simulation forecasted heightened, but sustained levels of primary and secondary protective immune responses to both vaccine candidates over time.\n                    <jats:italic>Ov<\/jats:italic>\n                    -103 was predicted to be non-camouflageable, as it lacked epitopes identical to protein sequences in the human proteome. Indeed, both antigens were able to bind with high affinity and activate the innate immune TLR4 receptor, implying efficient immune recognition. These findings suggest that\n                    <jats:italic>Ov<\/jats:italic>\n                    -RAL-2 and\n                    <jats:italic>Ov<\/jats:italic>\n                    -103 can induce sufficient protective responses through diverse humoral and cellular mechanisms. Overall, our study provides additional layer of evidence for advancing the clinical development of both vaccine candidates against onchocerciasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0312315","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T13:25:31Z","timestamp":1729517131000},"page":"e0312315","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["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"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-5705","authenticated-orcid":true,"given":"Derrick Neba","family":"Nebangwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-3894","authenticated-orcid":true,"given":"Robert Adamu","family":"Shey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Madulu","family":"Shadrack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cabirou Mounchili","family":"Shintouo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ntang Emmaculate","family":"Yaah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernis Neneyoh","family":"Yengo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Teke","family":"Efeti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketura Yaje","family":"Gwei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darling Bih Aubierge","family":"Fomekong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon Takop","family":"Nchanji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud Azonpi","family":"Lemoge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0795-394X","authenticated-orcid":true,"given":"Fidele","family":"Ntie\u2011Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Mbigha","family":"Ghogomu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"issue":";10159","key":"pone.0312315.ref001","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"SL James","year":"2018","journal-title":"The Lancet"},{"issue":"1","key":"pone.0312315.ref002","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1038\/s41598-019-40833-x","article-title":"In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases","volume":"9","author":"RA Shey","year":"2019","journal-title":"Scientific Reports"},{"issue":"7","key":"pone.0312315.ref003","doi-asserted-by":"crossref","first-page":"e497","DOI":"10.1371\/journal.pntd.0000497","article-title":"Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal","volume":"3","author":"L Diawara","year":"2009","journal-title":"PLoS Neglected Tropical Diseases"},{"issue":"Suppl 1","key":"pone.0312315.ref004","doi-asserted-by":"crossref","first-page":"S93","DOI":"10.1179\/000349802125000673","article-title":"APOC\u2019s strategy of community-directed treatment with ivermectin (CDTI) and its potential for providing additional health services to the poorest populations. 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