Journal article
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
PloS one, v 19(10), 0312315
21 Oct 2024
PMID: 39432476
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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, Ov-RAL-2 and Ov-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 Ov-RAL-2 and Ov-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 Ov-RAL-2 and Ov-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. Ov-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 Ov-RAL-2 and Ov-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.
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Details
- 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
- Creators
- Derrick Neba Nebangwa (Corresponding Author) - University of BueaRobert Adamu Shey - University of BueaDaniel Madulu Shadrack - St. John's University of TanzaniaCabirou Mounchili Shintouo - University of BueaNtang Emmaculate Yaah - University of BueaBernis Neneyoh Yengo - Drexel UniversityMary Teke Efeti - University of BueaKetura Yaje Gwei - University of BueaDarling Bih Aubierge Fomekong - University of BamendaGordon Takop Nchanji - University of BueaArnaud Azonpi Lemoge - Wilmington UniversityFidele Ntie-Kang - University of BueaStephen Mbigha Ghogomu - University of Buea
- Publication Details
- PloS one, v 19(10), 0312315
- Publisher
- PLOS
- Number of pages
- 29
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001339630700034
- Scopus ID
- 2-s2.0-85206960410
- Other Identifier
- 991022202523704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology