Envisioning Next Generation Immuno-Modulated, Multivalent COVID-19 DNA Vaccines

The first-generation COVID-19 vaccines were developed for rapid production and deployment and were not optimized for generating cellular responses that result in effective viral clearance. Though early data has indicated some of these vaccines to be over 95% effective, these first-generation vaccines were primarily designed to generate a strong antibody response and, while they have been shown to provide prophylactic protection against disease, the durability of this protection is currently unclear. The majority of these vaccines have been specifically developed to target wild-type or the D614G variant of SARS-CoV-2 spike (S) protein. It has been observed that the S protein is a locus for rapid evolutionary and functional change as evidenced by the emergence of alpha, beta, gamma, epsilon, and delta variants, among others. This propensity for mutation of the S protein leads to future risk of efficacy reduction over time as these mutations accumulate and more new variants develop.

Celsion’s next generation vaccine initiative stands at the confluence of immunotherapy and immunogenicity and envisions delivery, on a single plasmid, multiple SARS-CoV-2 antigens or variants and in some instances, in conjunction with a potent immune modifier(s) to improve the quality of humoral and/or cellular responses. While most COVID-19 vaccines in late-stage clinical development are monovalent (S antigen only), Celsion has taken this multivalent approach in an effort to generate an even more robust immune response that not only results in a strong neutralizing antibody response, but also a more robust and durable T-cell response.

Celsion’s vaccine candidate approach comprises a single plasmid vector containing the DNA sequence encoding more than one of the SARS-CoV-2 spike antigen variants , or a combination of spike antigen, with other potentially immunogenic antigens including the membrane (M) or nucleocapsid (N) antigen. Delivery will initially be evaluated intramuscularly with a non-viral synthetic DNA delivery carrier that facilitates vector delivery into the cells of the injected tissue and has potential immune adjuvant properties. Future iterations may include immune system modifiers, such as cytokines or chemokines, to further enhance durable immunogenicity.  Unique designs and formulations of Celsion’s vaccine candidates offer several key advantages.

  • Mulivalent pDNA: The multivalent design of the plasmid DNA (pDNA) candidate COVID-19 vaccine provides for the potential of broad-based protection and higher probability of resistance to mutational changes compared to single antigen vaccines.
  • Manufacturing, Storage & Distribution Advantages: Rapid antigen design, an established supply chain, timely manufacturing scale-up and cost-effective manufacturing leveraging existing processes and equipment with product stability that is compatible with standard vaccine storage and distribution models are key features of this flexible vaccine platform.
  • Enhanced Efficacy: Potent immune modifiers such as cytokines and chemokines may improve humoral and cellular responses to antigens and can be easily incorporated in the pDNA delivery system.