[PMC free content] [PubMed] [CrossRef] [Google Scholar] 2. to develop COVID-19 vaccines that provide long-term protection. KEYWORDS: SARS-CoV-2, spike glycoprotein, DNA vaccine, protein vaccine, non-human primate Introduction The COVID-19 pandemic has caused over 100 million cases of the novel coronavirus and over 22 million deaths globally. While public health measures such as social distancing have played important roles in controlling local outbreaks, the continued spread of COVID-19, especially in remote and underdeveloped areas around the world, Blasticidin S only extends the further threat of the pandemic. In addition, many countries have experienced new waves of transmission even after original outbreaks are brought under control. More definitive large scale public health measures like vaccines are the only hope for controlling the global COVID-19 pandemic [1, 2]. Over a dozen COVID-19 vaccines have entered Phase III clinical studies to establish efficacy for large Rabbit Polyclonal to REN scale public use. Several leading candidates are using Blasticidin S novel vaccine platforms such as viral vector [3C7] or mRNA [8C12] approaches, which showed exciting levels of protection efficacy in reports from completed Phase III studies [13, 14]. They have received or are expected to receive Emergency Use Authorization (EUA) by respective regulatory agencies. While their short-term safety has been established, the safety profiles of these vaccines in the long-term, as well as in larger and globally- diverse populations, have yet to be established. One other major type of COVID-19 vaccines under development is the inactivated vaccine approach [15C19]. Although no similar findings have been reported from the current inactivated COVID-19 vaccines, possible adverse events have been observed in the past with this type of vaccine [20, 21]. There are also potential biosafety issues associated with the need to produce large stocks of live SARS-CoV-2 viruses before inactivation. Inactivated vaccines are usually unable to induce cytotoxic T cell immunity (CTL). Traditional inactivated vaccines do not include adjuvants, but some COVID-19 vaccines have added adjuvant to further improve the immunogenicity [22]. At the same time, reports suggest that the SARS-CoV-2 infections may not lead to long-lasting immune responses and that some recovered patients may be re-infected again by the same virus [23C25]. Therefore, it is highly desirable to develop COVID-19 vaccines that are highly immunogenic and elicit long-lasting immunity. It is currently unknown whether any of the leading COVID-19 vaccines can meet such an objective. Additional novel approaches are needed to further enrich the COVID-19 vaccine pipeline to both provide a second generation of practical vaccines and learn more about the unique contributions of different technology platforms. In this study, we develop a unique subunit COVID-19 vaccine concept by combining the S full-length DNA plasmid and S1 recombinant protein to deliver them at the same time. This concept design is based on a significant body of literature accumulated over the past two decades, including our own work, that demonstrates the effectiveness of the DNA vaccine modality. In vivo production of encoded antigens from DNA immunization activates the endogenous Blasticidin S antigen processing and presentation pathway to effectively trigger helper T cell responses, which is critical for B cell development [26]. DNA-primed specific B cells can be further expanded with the addition of a protein component to produce a large amount of desired antibodies. In this study, our novel Covid-19 vaccine design is demonstrated to be more effective in the elicitation of higher immune responses, including neutralizing antibodies and T cell responses, than the use of either DNA or protein component alone. This combination vaccine was also able to elicit full protection against the challenge of SARS-CoV-2 in a non-human primate (NHP) model, which has not been achieved in previous reported COVID-19 vaccine studies in similar NHP models [6, 27C30]. Materials.