Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19

Emerg Microbes Infect. 2021 Dec;10(1):1574-1588. doi: 10.1080/22221751.2021.1959270.

Abstract

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Keywords: COVID-19; SARS-CoV-2; adenovirus; antibody; immune response; vaccine.

MeSH terms

  • Adenoviridae / genetics*
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • COVID-19
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / genetics
  • COVID-19 Vaccines / immunology*
  • Chlorocebus aethiops
  • Female
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Immunogenicity, Vaccine
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred BALB C
  • Pan troglodytes / virology
  • Protein Binding
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / administration & dosage
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vaccination
  • Vero Cells

Substances

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

Grants and funding

This work was supported by the National Program on Key Research Project of China [Grant Number 2020YFA0907100]; Chinese Academy of Sciences (CAS) Project for Young Scientists in Basic Research [Grant Number YSBR-010]; Strategic Priority Research Program of the CAS [Grant Number XDB29010202]; National Natural Science Foundation of China (NSFC) [Grant Numbers 81991494], [Grant Number 32041010]; China Postdoctoral Science Foundation [Grant Number 2020T130031ZX]; Youth Innovation Promotion Association CAS [Grant Numbers 2018113], [Grant Number 2017122]; Hainan Province Postdoctoral Science Fund of China [Grant Number 2019-20741].