Administration of DNA Vaccines with DNA Encoding Ii-PADRE Generates Potent PADRE-specific CD4+ T-cell Immune Responses and Enhances Vaccine Potency

Unmet Need: DNA vaccine technology is a desirable antiviral and cancer immunotherapeutic strategy for its simple design and cost-effective implementation. However, current DNA vaccine programs are hindered by poor immunogenicity.

Technical Details: Johns Hopkins researchers have designed a novel fusion construct to enhance immunogenicity to DNA vaccines. Increased DNA vaccine potency is achieved by coordinated administration with a recombinant DNA encoding the invariant chain protein (Ii) that associates with an MHC class II molecule and replaces MHC class II associating peptide region (CLIP) with a potent CD4+ T-cell activating peptide PADRE (invariant Pan HLA-DR reactive epitope).  As shown in mice, Ii-PADRE potently and specifically increases CD4+ T-cell responses that in turn generate increased effector CD8+ T-cell functions against viral infection or cancer. To further enhance CD4+ T-cell responses using Ii-PADRE, DNA encoding MHC class II co-activating protein CIITA is included in administration to increase transcription of MHC class II complexes. Together, administration of Ii-PADRE, CIITA and a DNA vaccine of interest leads to increased anti-viral or anti-tumor responses generated from DNA vaccines.

Value Proposition:
 

• Novel DNA vaccine adjuvant to extensively enhance immune response
• Suitable as an adjunct therapy to enhance effectiveness of traditional chemotherapy
• Inexpensive and efficient production of enhancing components due to nucleic acid composition
• Broad application of technology for both human and animal disease intervention

Looking for Partners to: Develop & commercialize the technology as an immune enhancement strategy for DNA vaccines targeted against viral infection or cancer.

Stage of Development: Pre-Clinical

Data Availability: Animal data

Inventors: T.C. Wu, Chien-Fu Hung

Patent Status: Issued: US9,085,638

Publication(s): Hung CF, Tsai YC, He L, Wu TC. (2007) DNA Vaccines Encoding Ii-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency. Mol Ther 15(6): 1211-1219.

 

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