COVID-19 vaccine development research

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The urgent need for a vaccine to combat the COVID-19 pandemic prompted us to apply our decades of experience in developing HIV vaccines towards SARS-CoV-2. We hypothesize that lessons learned from past SARS vaccine research, including HIV vaccine research, could be applied to the design of a COVID-19 vaccine. Based on the high convalescence rate, the human immune system is able to control and eliminate the virus infection, thus it is likely that a vaccine will work. Recent data from several clinical trials showed that different vaccine platforms showed that induction of humoral immune responses is possible. In support of this, it was reported that SARS-CoV infected persons developed durable virus-specific (N, S, M, E) T cell responses and strong T cell responses targeting S correlated with higher neutralizing Ab activity. Based on the persistence mechanisms known for other viruses, we hypothesize that SARS-CoV-2 may also have developed strategies to evade the host's immune system. Thus, an effective vaccine may require design beyond the use of natural proteins and we are exploring both avenues. One common mechanism of immune evasion is rapid mutation of antigenic targets, leading to immune escape. Our vaccine strategy aims to induce protective immune responses targeting structurally conserved portions of the SARS-CoV-2 S and N proteins that are also important for protective immunity. This strategy is an important addition to the on-going vaccine efforts, in case there are problems with the first generation of vaccines that have moved or are moving to phase I clinical trials. This vaccine effort may also offer an advantage by inducing broader immunity able to recognize a broader range of coronaviruses. We are developing DNA-based vaccines based on inclusion of regions of structural importance, based on X-ray crystallographic data of SARS1 and SARS-CoV-2 structures, with the aim to induce more effective immune responses. We have long practical experience in the development and application of DNA vaccine regimens. We use this vaccine platform due its versatility, simplicity, scalability, and lack of eliciting immunity against the vector. The use of a nucleic acid-based vaccine provides a simple method allowing efficient expression and post-translational modifications of structurally complex immunogens and results in the development of both humoral and cellular immunity. Immune responses can be maintained for long periods and can be boosted by the same or heterologous boosting strategies. Over many years we have successfully optimized different steps to obtain improve immunogenicity including optimized vaccine regimens, vaccine delivery, immunogen selection, adjuvant selection, and combination vaccine regimens. We have developed a panel of CoV2 DNA vaccines. Testing in macaques has shown induction of robust Ab responses including Nab responses comparable of CoV-2 infected convalescent patients as well as strong T cell responses. We are in the process of testing efficacy of our initial vaccine candidates.