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

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 HungHui 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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2724-2734
Number of pages11
JournalEmerging Microbes and Infections
Volume11
Issue number1
DOIs
StatePublished - Dec 31 2022
Externally publishedYes

Keywords

  • SARS-CoV-2
  • neutralizing antibody
  • non-human primate
  • protection
  • subunit vaccine

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

Fingerprint

Dive into the research topics of 'A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2'. Together they form a unique fingerprint.

Cite this