A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates

Emerg Microbes Infect. 2022 Dec;11(1):1058-1071. doi: 10.1080/22221751.2022.2056524.

Abstract

Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and non-human primates, and elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 μg or 50 μg ZF2001 prevented infection with SARS-CoV-2 in lung, trachea, and bronchi, with milder lung lesions. No evidence of disease enhancement was observed in both animal models. ZF2001 has been approved for emergency use in China, Uzbekistan, Indonesia, and Columbia. The high safety, immunogenicity, and protection efficacy in both mice and NHPs found in this preclinical study was consistent with the results in human clinical trials.

Keywords: Covid-19; antibody; immune response; subunit protein vaccine; zf2001.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Carrier Proteins
  • Humans
  • Immunogenicity, Vaccine
  • Mice
  • Mice, Inbred BALB C
  • Primates
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • Vaccines, Subunit

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Carrier Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Subunit
  • spike protein, SARS-CoV-2

Grants and funding

This work is supported by the National Program on Key Research Project of China [2020YFA0907100 and 2020YFC0842000], the National Natural Science Foundation of China, China (NSFC) [81991494 and 82122031], the intramural special grant for SARS-CoV-2 research from the Chinese Academy of Sciences and Anhui Zhifei Longcom Biopharmaceutical. Lianpan Dai is supported by NSFC [82122031] Youth Innovation Promotion Association [2018113] and CAS Project for Young Scientists in Basic Research (YSBR-010).