A New Era for DNA Vaccines? Imunon’s PlaCCine DNA Platform

The global response to the COVID-19 pandemic highlighted the incredible power of nucleic acid vaccines, particularly the rapid development and deployment of mRNA vaccines. However, it also brought to light some significant challenges with existing technologies, such as their ultra-cold-chain requirements for storage and distribution, susceptibility to degradation, and potential for reactogenicity and hyperimmune reactions associated with lipid carriers. These factors contribute to high manufacturing costs and hinder equitable global access, especially in developing countries.

            PlaCCine, a novel DNA-based vaccine platform that aims to address these limitations while offering robust protection against infectious diseases was developed by Imunon, Inc., Lawenceville, NJ.  Imunon, Inc. is a clinical-stage biotechnology company pioneering the development of novel immunotherapies and nucleic acid-based vaccines to treat cancer and infectious diseases. Leveraging proprietary delivery technologies, Imunon has built two key platforms: TheraPlas™, focused on plasmid DNA-based therapies for solid tumors, and PlaCCine™, a next-generation DNA vaccine platform designed to overcome many of the limitations of traditional mRNA vaccines. The company has pipeline of therapeutic candidates that address urgent public health needs—ranging from COVID-19 to emerging viral threats and oncologic indications—while simplifying manufacturing and distribution through temperature-stable, non-lipid formulations.

            PlaCCine distinguishes itself by utilizing a device- and vector-free chemical delivery system, simplifying administration and potentially reducing overall costs. This system involves a DNA plasmid encoding the target antigen, formulated with a functionalized poloxamer and an adjuvant, AlPO₄, which protects the DNA from degradation and facilitates its uptake into muscle cells.

            The poloxamer is a nonionic triblock copolymer composed of polyoxypropylene and polyoxyethylene, and it is covalently modified with a metal chelator. Its unique structure features a central hydrophobic chain connected to two hydrophilic chains, which include functional molecules. When the DNA plasmid encoding the target antigen is formulated with this functionalized poloxamer and an adjuvant, AlPO4, the poloxamer plays a crucial role in protecting the DNA from degradation by extracellular nucleases. This protective action increases the DNA's bioavailability, making it more accessible for cellular uptake. Furthermore, it facilitates the uptake of DNA into muscle cells after direct injection by interacting with the cell membrane, and enhances DNA distribution through tissue, ultimately leading to durable gene expression and robust immune responses.

            One of PlaCCine's most compelling advantages is its temperature stability, making it suitable for global distribution without the stringent cold-chain demands of mRNA vaccines. Furthermore, unlike multivalent mRNA vaccines that require separate manufacturing for each mRNA component, PlaCCine can incorporate multiple antigen targets into a single plasmid, potentially reducing production costs and time—a critical factor in responding to rapidly emerging viral variants. Its non-lipid composition may also offer safety advantages, reducing the reactogenicity and anaphylaxis sometimes associated with mRNA vaccines.

            In this research led by Inunon, PlaCCine's effectiveness in non-human primate models was investigated, directly comparing it to Moderna's mRNA-1273 vaccine. The findings offer valuable insights:

• Humoral Immune Responses (Antibodies):

  • The Moderna mRNA-1273 vaccine (100 µg dose) consistently elicited significantly higher binding (IgG) and neutralizing antibody titers against the SARS-CoV-2 spike antigen in non-human primates. For instance, mRNA-1273 led to a peak mean IgG titer of 170,681 and a peak mean IC50 (neutralizing antibody) titer of 6,480.

  • In contrast, the PlaCCine pvac15 vaccine (1 mg dose) achieved a peak mean IgG titer of 5,020, and the pvac16 vaccine (2 mg dose) reached 9,614. Their respective neutralizing antibody titers were 100 (pvac15) and 140 (pvac16). The study noted that variability in PlaCCine groups' antibody titers might be due to smaller sample sizes.

• Cellular Immune Responses (T-cells):

  • Here, PlaCCine showed a notable advantage. The pvac16 immunization induced robust SARS-CoV-2 antigen-reactive T cell responses, peaking at 174 SFU/million cells before challenge. This response primarily involved CD28+/CCR7+/CD45RA-/CD8+ central memory T cells, indicating a durable cellular immune response.

  • The mRNA-1273-induced T cell response had a lower peak value of 48 SFU/million cells.

• Protective Efficacy (Viral Clearance):

  • Despite the differences in antibody titers, the magnitude and rates of viral clearance were comparable between the PlaCCine and mRNA-1273 vaccinated animals.

  • In both PlaCCine (pvac15 and pvac16) and mRNA-vaccinated non-human primates, nasal and bronchoalveolar lavage (BAL) viral loads were rapidly and completely reduced to undetectable levels within two days post-challenge. This rapid clearance indicates durable protection conferred by both vaccine types. Control animals, conversely, maintained high viral loads for a longer period. This suggests that the immune response generated by PlaCCine, including its strong cellular component, is sufficient to provide effective in vivo protection.

The PlaCCine platform also demonstrated impressive efficacy against the Omicron XBB1.5 variant in human ACE2 transgenic mice. All immunized animals were completely protected from morbidity and mortality, showing no significant weight loss and undetectable replication-competent virus in their lungs after challenge. Non-immunized animals, on the other hand, experienced significant weight loss and died within seven days.

            These promising preclinical results in both non-human primates and mice highlight the potential of the PlaCCine platform as a viable alternative to existing nucleic acid vaccines. Its practical advantages in terms of stability, ease of manufacturing, potential for multivalency, and safety profile make it particularly attractive for widespread global use. The IMNN-101 vaccine, targeting the XBB1.5 variant, is currently undergoing a Phase I clinical trial in healthy human volunteers, marking a significant step towards bringing this innovative technology to human use.

Sood S, Gary EN, Matar M, Kim J, Hojecki CE, Warner B, Vendramelli R, Truong T, Smith A, Rice J, Sparks J, DeSalvo M, Henderson J, Rogers JA, Sharma A, Pessaint L, Iavarone CA, Kobasa D, Boyer JD, Lindborg S, Anwer K. Intramuscular DNA vaccine provides protection in non-human primate and mouse models of SARS-CoV-2. Front Immunol. 2025 Jun 6;16:1589584. doi: 10.3389/fimmu.2025.1589584. PMID: 40547007; PMCID: PMC12179688.

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1589584/full