A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2
| Autor: | Shixia Wang, Chang Yi Wang, Hui-Kai Kuo, Wen-Jiun Peng, Juin-Hua Huang, Be-Shen Kuo, Feng Lin, Yaw-Jen Liu, Zhi Liu, Huang-Ting Wu, Shuang Ding, Kou-Liang Hou, Jennifer Cheng, Ya-Ting Yang, Ming-Han Jiang, Min-Sheng Wang, Tony Chen, Wei Guo Xia, Ed Lin, Chung Ho Hung, Hui-Jung Chen, Zhonghao Shih, Yi Ling Lin, Valorie Ryan, Mei Mei Hu, D. Gray Heppner, Delphine C. Malherbe, Sivakumar Periasamy, Natalia Kuzmina, Chandru Subramani, Michael Hellerstein, Thomas P. Monath, Alexander Rumyantsev, Alexander Bukreyev, Farshad Guirakhoo |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Emerging Microbes and Infections, Vol 11, Iss 1, Pp 2724-2734 (2022) |
| Druh dokumentu: | article |
| ISSN: | 22221751 2222-1751 |
| DOI: | 10.1080/22221751.2022.2140608 |
| Popis: | The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague–Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster. |
| Databáze: | Directory of Open Access Journals |
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