Journal Article

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2

Chen, Tony, Jiang, Ming-Han, Rumyantsev, Alexander, Liu, Zhi, Periasamy, Sivakumar, Huang, Juin-Hua, Cheng, Jennifer, Lin, Ed, Heppner, D. Gray, Subramani, Chandru, Xia, Wei Guo, Peng, Wen-Jiun, Wang, Chang Yi, Yang, Ya-Ting, Hung, Chung Ho, Kuo, Hui-Kai, Monath, Thomas P., Lin, Yi Ling, Malherbe, Delphine C., Kuo, Be-Shen, Ryan, Valorie, Kuzmina, Natalia, Hellerstein, Michael, Lin, Feng, Ding, Shuang, Guirakhoo, Farshad, Hou, Kou-Liang, Chen, Hui-Jung, Wu, Huang-Ting, Shih, Zhonghao, Wang, Shixia, Bukreyev, Alexander, Hu, Mei Mei, Liu, Yaw-Jen, Wang, Min-Sheng

2022

Overview

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.

• Publisher: Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
• Subject: Coronaviruses / COVID-19 vaccines / neutralizing antibody / non-human primate / Peptides / protection / Proteins / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / subunit vaccine