Intradermal-delivered DNA vaccine induces durable immunity mediating a reduction in viral load in a rhesus macaque SARS-CoV-2 challenge model

Cell Rep Med. 2021 Oct 19;2(10):100420. doi: 10.1016/j.xcrm.2021.100420. Epub 2021 Sep 28.

Abstract

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.

Keywords: COVID-19; ID DNA vaccine; SARS-CoV-2; challenge; coronavirus; electroporation; infectious disease; macaque; protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / therapeutic use
  • Female
  • Injections, Intradermal
  • Lung / virology*
  • Macaca mulatta
  • Male
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / metabolism
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / therapeutic use
  • Viral Load

Substances

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