Next-generation DNA-LNP vaccines show promise for long-lasting immunity

A team of researchers from The Wistar Institute, the University of Pennsylvania, and INOVIO has developed a novel DNA vaccine technology that incorporates lipid nanoparticles (LNPs) for improved immune response and long-lasting immunity. The study, published in Cell Reports Medicine, demonstrates the potential of DNA-LNP vaccines as a next-generation immunization platform.

Enhancing DNA vaccine stability with lipid nanoparticles

Lipid-based delivery systems have proven effective for RNA-based vaccines, but DNA formulations have struggled with stability and efficacy. The research team, led by Wistar’s Nicholas Tursi, explored modifications to LNP formulations to better stabilize and deliver DNA payloads. Their findings highlight that optimizing the balance between lipid nanoparticles and DNA structures significantly improves vaccine-induced immune responses.

Stronger and longer-lasting immunity

Using a model influenza DNA-LNP vaccine, researchers observed that optimized formulations produced smaller, more stable particles, leading to stronger immune activation. The DNA-LNP vaccines triggered unique early immune responses compared to traditional mRNA or protein-based vaccines.

Key findings include:

  • Durable immune memory: A single dose of the DNA-LNP vaccine generated antibody and T cell responses that lasted beyond a year in small animal models.

  • Cross-species efficacy: In a rabbit model, strong and sustained immune responses were observed.

  • Protection against COVID-19: A DNA-LNP vaccine encoding the SARS-CoV-2 spike protein prevented morbidity and mortality in a live virus challenge.

A new frontier in vaccine development

DNA vaccines have traditionally required specialized delivery devices to ensure effective cellular uptake. The incorporation of LNPs offers a simpler alternative that may enable administration via standard needle and syringe while enhancing immune responses.

With the ability to trigger robust, long-lived immunity, DNA-LNP vaccines could complement existing vaccination strategies or emerge as a leading immunization technology. Continued research and development will determine their potential in future vaccine applications.