DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss

Abstract

The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a nucleic acid-based vaccine is a novel option, beyond the traditional inactivated virus vaccine or recombinant protein vaccine. Here, we report a DNA vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19.

A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection

“…We have previously applied an EP device for use in animals to deliver the SARS-CoV-2 DNA vaccine, which has a protective effect against SARS-CoV-2 infection in hamsters 14 . A suitable delivery system to enhance DNA vaccine efficacy is required to bridge the gap between the development phase and clinical study.…”

“…Our previous studies showed that a DNA vaccine with the tumor-associated antigen L6 followed by EP could induce cellular immunity against cancer growth 13 . We further applied this approach for COVID-19, and the DNA-encoded full-length spike (S) protein of SARS-CoV-2 (pSARS2-S) was shown to induce protective immune responses against viral challenge in hamsters 14 . EP combined with DNA vaccination greatly increases the efficacy of DNA vaccines 3 – 5 .…”

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model

“…In this work, we evaluated the protective efficacy of a pcDNA3.1 vectored SARS-CoV-2 spike antigen fused with and without CD40L in a SARS-CoV-2 Syrian hamster challenge model. It is noted in the literature that doses of DNA vaccines vary, ranging from 50 to 200 µg with or without the use of alternative DNA vaccine delivery methods (45)(46)(47). In this study, we employed a 100 µg dose, as our study was mainly intended to compare the vaccines with or without CD40 ligand.…”

Insights into COVID-19 Vaccine Development Based on Immunogenic Structural Proteins of SARS-CoV-2, Host Immune Responses, and Herd Immunity

“…Nevertheless, current plasmid DNA vaccines often rely on a kanamycin-based selection marker, which is not generally used to treat bacterial infection in human. Considering such pros and cons, a DNA vaccine for SARS-CoV-2 is being developed and tested in preclinical and clinical studies [ 70 ]. ZyCoV-D, developed by Ahmedabad (headquarter)-based Zydus Cadila, and approved by DCGI, India, is the first plasmid DNA vaccine for SARS-CoV-2 in humans, and is currently undergoing clinical trial (CTRI/2020/07/026352)./).…”