Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2

Abstract

Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies.

Safety and immunogenicity of two recombinant DNA COVID-19 vaccines containing the coding regions of the spike or spike and nucleocapsid proteins: an interim analysis of two open-label, non-randomised, phase 1 trials in healthy adults

“…Previous studies on DNA vaccines have determined that the number of doses required for effective vaccination is dependent on the antigen and virus types and how they interact with the immune system. 25 One to two doses of the DNA vaccine are enough to elicit sufficient neutralising antibody responses to the influenza virus, whereas three to four doses are needed to produce protective humoral responses against HIV. 26 In a preclinical study on a plasmid DNA vaccine for SARS-CoV-2, the magnitude of binding and neutralising antibody responses was the highest after three doses.…”

“… 26 In a preclinical study on a plasmid DNA vaccine for SARS-CoV-2, the magnitude of binding and neutralising antibody responses was the highest after three doses. 25 Future studies on humoral immunogenicity after another booster dose of GX-19N are required.…”

Sustainable Healthcare: Exploring Renewable Energy Integration and Technological Innovations in Sustainable Healthcare Aligned with Islamic Principles and UAE Initiatives

“…Health care professionals can create awareness among general public regarding Covid-19 vaccination also clarify their doubts on Covid-19 vaccination. We can save our community and the whole world from Covid-19 pandemic through vaccination [1][2][3][4][5][6][7][8][9][10].…”

Safety and immunogenicity of a recombinant DNA COVID-19 vaccine containing the coding regions of the spike and nucleocapsid proteins: Preliminary results from an open-label, phase 1 trial in healthy adults aged 19–55 years

“…Previous studies on DNA vaccines have determined that the number of doses required for effective vaccination is dependent on the antigen and virus types and how they interact with the immune system. 22 One to two doses of the DNA vaccine are enough for eliciting sufficient neutralizing antibody responses to influenza virus, whereas three to four doses are needed to produce protective humoral responses against HIV. 23 In a preclinical study of a plasmid DNA vaccine for SARS-CoV-2, it was reported that the magnitude of binding and neutralizing antibody responses was the highest after three doses.…”

“…23 In a preclinical study of a plasmid DNA vaccine for SARS-CoV-2, it was reported that the magnitude of binding and neutralizing antibody responses was the highest after three doses. 22 Further studies on humoral immunogenicity after another booster dose of GX-19N should be considered.…”