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.
Highlights
In the 21st century, three coronaviruses that have evolved the ability to cross the species barrier and infect humans have been identified: severe acute respiratory disease syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS)-CoV, and, most recently, SARS-CoV-2
No licensed vaccine against SARS-CoV-2 or any other human coronaviruses exists, several SARS-CoV-2 vaccine platforms, including inactivated virus, viral vector vaccine, plasmid (p)DNA, and messenger RNA, are being tested at various stages in clinical trials [1,2,3,4,5,6] with two mRNA vaccines being approved for emergency use [7,8]
The S1 subunit consists of four domains, namely, the N-terminal domain (NTD), the C-terminal domain (CTD), and subdomains II and I
Summary
In the 21st century, three coronaviruses that have evolved the ability to cross the species barrier and infect humans have been identified: severe acute respiratory disease syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS)-CoV, and, most recently, SARS-CoV-2. No licensed vaccine against SARS-CoV-2 or any other human coronaviruses exists, several SARS-CoV-2 vaccine platforms, including inactivated virus, viral vector vaccine, plasmid (p)DNA, and messenger RNA (mRNA), are being tested at various stages in clinical trials [1,2,3,4,5,6] with two mRNA vaccines being approved for emergency use [7,8]. As with all human coronaviruses, the S protein is the primary antigenic determinant responsible for eliciting antibodies that function to prevent viral entry and fusion [13]. Human immunity against coronaviruses is primarily mediated by the production of neutralizing antibodies at levels that are sufficient to confer protection from reinfection [13]
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