Title : Immunogenicity of DNA Vaccines based on Multicistronic Vectors and Synthetic DNA Delivery Systems
Abstract:
Nucleic acid-based vaccines represent an attractive alternative to live attenuated and subunit-based vaccines due to their capacity to trigger both humoral and cellular immunity and potential for low-cost and shortened production processes. The fast-track approval and the worldwide vaccination programs for Covid-19 pandemic underscores the efficacy and safety of these novel class of vaccines. DNA and RNA vaccines have been recognized to provide an efficient protection without significant safety risk. Despite the recent successes in Covid-19 vaccines there is strong rationale to continue the investigations of other vaccine strategies to address the need for emergence of new variants (Covid-19), uncontrolled outbreak (flu), the demand for infectious diseases with an unmet need (CMV, RSV), and the requirement for diseases demanding diversified immune response (malaria). Our DNA-based vaccine approach encompasses molecular elements that are designed to improve the breadth of immune response by targeting multiple antigens of a pathogen or multiple mutants of the same antigen, improve the intrinsic adjuvanticity of the vaccine as needed by co-expressing a potent molecular adjuvant particularly against pathogens where conventional vaccines are poorly immunogenic, promote uptake and chemical adjuvanticity of the DNA vaccine with the use of synthetic delivery system, prolong vaccine shelf-life and stability at working temperatures, and utilize an existing cost-effective and scalable process that can be rapidly functional in case of a new outbreak or an evolving existing pandemic. To that end, we have initially produced a family of DNA vaccine vectors expressing one or more of SARS-CoV-2 surface antigens as a proof-of-concept target, verified vector composition, and demonstrated expression of the encoded genes. We have also developed an intramuscular vaccine formulation based on a covalently modified co-polymer that yields high levels of a reporter gene expression within 24 hours after treatment, a critical time window for immune activation, followed by durable expression potentially conducive to B- and T-cell responses. Immunization of Balb-C mice with a plasmid expressing the Spike protein of SARS-CoV-2, resulted in the production of IgG antibodies with evidence of viral neutralization and cytotoxic T-cell response specific to the antigen. Parallel in vivo studies are in progress to optimize vector and antigen design, improve the delivery system, explore alternative route of administration, identify the optimal vaccine dose and regimen. The current data and results from the ongoing studies will be presented at the conference.
