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

Abstract

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (ID)-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.

Robust and protective immune responses induced by heterologous prime‐boost vaccination with DNA‐protein dimeric RBD vaccines for COVID‐19

“…8 ZyCoV-D, INO-4800, and pSARS2-S, carrying the SARS-CoV-2 spike gene, induced protective immune responses in animals. [9][10][11] COVID-eVax, encoding secreted monomeric SARS-CoV-2 RBD, induced stronger antibody responses than DNA vaccine candidates encoding full-length S protein and S1 subunit protein. 12 COVID-eVax has been demonstrated to confer mice and ferrets substantial protection against the SARS-CoV-2 challenge.…”

Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in rhesus macaques against SARS‐CoV‐2

“…Needle‐free injectors for DNA vaccine delivery have been found to augment the immune response, possibly by enhancing the dispersion of injecting substances or increasing local inflammation 39 . Multiple approaches have been tried by various groups for vaccine delivery in the case of SARS‐CoV‐2 DNA vaccines like intramuscular, intradermal, oral, and electroporation techniques 28,31,32,40 . The use of the electroporation method for GX‐19 vaccine candidate delivery enhanced the antibody and T cell response in NHP's 31 …”

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques

“…Another study in mice showed that the second dose of protein immunization, based on intradermal immunization with a novel inactivated coronavirus vaccine, protected mice from challenge infection with a mutant strain [11] . Based on the above analysis, we hypothesized that intradermal immunization might provide a new approach or strategy to solve the problem that anti-novel coronavirus antibodies are not durable or that variant strains can escape immune protection [18] , [19] , [20] . Because rhesus monkeys are similar to humans in anatomy and organ function and their biological characteristics are reliable, genetic background is relatively stable, adaptability is strong, and background information is abundant, they are widely used in pharmacology and toxicology studies [21] , [22] .…”