Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon.
Tropical Disease Interventions, Diagnostics, Vaccines and Therapeutics (TroDDIVaT) Initiative, Buea, Cameroon.
PLoS One. 2024 Oct 21;19(10):e0312315. doi: 10.1371/journal.pone.0312315. eCollection 2024.
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.
盘尾丝虫病（河盲症）是一种使人虚弱的热带疾病，会导致严重的眼部和皮肤损伤，影响全球数百万人。随着全球防治工作从疾病管理转向消除，疫苗已成为至关重要的补充工具。非洲盘尾丝虫病疫苗倡议（TOVA）于 2015 年成立，旨在推进至少一种疫苗候选药物，最初针对 5 岁以下婴幼儿期的盘尾丝虫病，到 2025 年完成 I 期人体临床试验。值得注意的是，在临床前开发过程中，Ov-RAL-2 和 Ov-103 抗原表现出巨大的潜力，但由于某些不良反应和免疫原性限制，疫苗候选物在临床开发过程中的总体成功率仍然相对较低。因此，本研究旨在临床前试验之前预测 Ov-RAL-2 和 Ov-103 潜在盘尾丝虫病疫苗候选物的安全性和免疫原性。应用先进的分子模拟模型和分析免疫信息学算法来预测这些抗原在人类中的潜在不良反应和疗效。分析表明，Ov-RAL-2 和 Ov-103 均具有良好的安全性，因为在每个抗原中都未发现毒性和过敏表位。此外，两种抗原均预测含有大量不同表位（抗体、细胞因子和 T 细胞表位），这些表位与对盘尾丝虫病的保护性免疫有关。同样，虚拟疫苗接种模拟预测，随着时间的推移，两种疫苗候选物的初级和次级保护性免疫反应都会升高，但保持持续水平。Ov-103 预测为不可伪装的，因为它缺乏与人类蛋白质组中蛋白质序列相同的表位。事实上，两种抗原都能够与高亲和力结合并激活先天免疫 TLR4 受体，表明有效的免疫识别。这些发现表明，Ov-RAL-2 和 Ov-103 可以通过多种体液和细胞机制诱导足够的保护性反应。总体而言，我们的研究为推进这两种盘尾丝虫病疫苗候选物的临床开发提供了额外的证据。
