ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicExploring Immune Evasion and Vaccine Strategies in Host-Pathogen InteractionsView all 3 articles
In Silico Design of Novel Precision Vaccine Targeting Sclerostin Epitopes for Osteoporosis Prevention and Treatment
Provisionally accepted
- 1Shenzhen University, Shenzhen, China
- 2Shenzhen University General Hospital, Shenzhen, China
- 3Xi'an Jiaotong University, Xi'an, China
- 4The Health Service Center of Weifang Community, Shanghai, China
- 5Shenzhen Hospital, The University of Hong Kong, Shenzhen, China
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ABSTRACT Background: Osteoporosis has become an increasingly pressing global public health challenge. Monoclonal antibody romosozumab (ROMO), which targets sclerostin (SOST), a critical inhibitor of bone formation, demonstrates considerable therapeutic efficacy. However, its high cost and associated cardiovascular adverse events limit its widespread clinical adoption. Current preventive measures remain inadequate. Methods: This study presents a novel, cost-effective osteoporosis vaccine with dual preventive and therapeutic capabilities, derived from the high-affinity binding epitope of ROMO to SOST. ELISA screening identified SOST131-163 region as the primary binding epitope for ROMO, situated within loop3 domain, enabling skeletal regulation without affecting cardiovascular system. SOST131-163 was conjugated to the diphtheria toxin translocation domain (DTT) to create novel SOST-targeted vaccines. Results: Immunogenicity assays demonstrated that both DDT-SOST(131-163)3 (DS3) and DDT-SOST(131-163)5 (DS5) elicited strong IgG2 antibody responses comparable to ROMO. Molecular docking studies indicated strong affinities of DS3 and DS5 for Toll-like receptor 2 (TLR2), enhancing TLR2-mediated humoral B-cell immunity and eliciting synergistic T-helper cell responses. Recombinant expression in Escherichia coli confirmed the successful production of DS3 and DS5, with molecular weights of 31.8 kDa and 40.3 kDa, respectively. In vivo experiments showed that the vaccines effectively induced high-titer anti-SOST antibodies in mice, overcoming immune tolerance. Additionally, cell-based assays indicated that antiserum from vaccinated mice inhibited osteoclast differentiation and promoted osteoblast mineralization. Conclusion: The SOST-targeted vaccination strategy offers a promising and cost-effective approach for the early prevention and sustained management of osteoporosis, demonstrating substantial potential for clinical translation.
Keywords: Osteoporosis, Sclerostin (SOST), Romosozumab (ROMO), Vaccine, Translocation domain of diphtheria toxin (DTT)
Received: 10 Jun 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Luo, Wu, Guan, Li, Yang and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huiren Tao, 1910244002@email.szu.edu.cn
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