An Adjuvanted / Targeted Nanoparticle-Based Platform for Genetic Vaccination
P. Daftarian, V. Lemmon, A. Kaifer, V. Perez, W. Li
Problem
Current methods for genetic immunization are challenged by poor in vivo delivery of multi-nucleotides into the cell/nucleus, weak immune responses and safety concerns, in particular for viral vectors.
Solution
Current approaches to vaccine design have shown that vaccines which mimic natural antigens to be produced in their native conformations are most effective in generation of functionally relevant immune response. Since use of live virus as vaccine is not practical for many applications, recent approaches to vaccine design have focused on the use of DNA vaccines. These vaccines present a broader repertoire of epitopes in a more physiologically relevant form which more closely resemble that seen in active infection, and are expected to induce stronger and more lasting humoral and cellular immunity, and presumably afford a greater degree of protection to subsequent infection. Unfortunately, in vivo delivery of DNA by current methods has poor in vivo transfection frequency, targets all cells including non-professional antigen presenting cells, and does not induce robust immune responses, therefore limiting the usefulness of genetic immunization. The present technology is a novel targeted/adjuvanted nanoparticle-DNA delivery platform which will specifically bind and transfect Antigen Presenting Cells (APC) and induce innate immune responses via activation of T helper cells whereby inducing strong immune responses.
Competitive Advantage
This unique technologies targets/uses host antigen-presenting-cells, in vivo, makes them express the antigen(s) of interest and activates CD4 T helper cells.
Applications
" a platform for genetic vaccination;
" a kit for generation of monoclonal antibodies (mAbs) that eliminates the need for protein purification. This kit consists of the proposed platform that may be mixed with any mammalian plasmid (vector) that includes the gene of interest.
Patent Status
PCT patent application was filed April 1, 2010.
Licensing Opportunity
We are seeking a commercialization partner with capabilities in product development, sales, and marketing. An exclusive license is available.
Selected References
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Pirouz Daftarian et al., Improved Protein-Free Methods for the Generation and Screening of Monoclonal Antibodies: Use of Nucleic Acid-Based Delivery and Rapid HTP Infrared-Based Assay. Meeting the Challenge of Delivery, Safety and Efficacy. Pal Talk 2009, San Diego, Ca. http://www.chi-peptalk.com/ptt.asp. http://www.infoshop-japan.com/conference/peptalk09/nab_day1.shtml
Marc Mansour, Bill Pohajdak, W Martin Kast, Antar Fuentes-Ortega, Ella Korets-Smith, Genevieve M Weir, Robert G Brown, and Pirouz Daftarian. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMaxﾮ. Journal of Translational Medicine 2007, 5:20.
Pirouz Daftarian, Marc Mansour, Bill Pohajdak, Antar Fuentes-Ortega, Ella Korets-Smith, Lisa MacDonald, Genevieve Weir, Robert G. Brown, and W. Martin Kast. . Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMaxﾮ encapsulated CTL/T helper peptides. Journal of Translational Medicine 2007, 5:26.
Guang-Yun Song,..Pirouz Daftarian, Zhongde Wang, Don Diamond and Joshua D. I. Ellenhorn. An MVA vaccine overcomes tolerance to human p53 in mice and humans. Cancer Immunology, Immunotherapy. 2007, 56:11931205
Pirouz Daftarian., &and W. Martin Kast. Eradication of established HPV 16-expressing tumors by a single administration of a vaccine composed of a liposome-encapsulated CTL-T helper fusion peptide in a water-in-oil emulsion. Vaccine, 2006, 24: 5235-5244.
Daftarian, Pirouz; Mansour, Marc; Fuentes-Ortega, Antar; Korets-Smitha, Ella; Brown, Robert G.; Martin Kast, W; Pohajdak, Bill. Treatment of Melanoma by the Simultaneous Administration of CTL T-Helper Epitope-Containing Peptides From P53 And Trp-2 in Vaccimax. Journal of Immunotherapy: 2006 - Volume 29 - Issue 6 - p 646
Pirouz Daftarian, et. al. Nucleotides-Based Immunization: Comparison of Water-In-Oil Liposome-Based Delivery of Nucleotides with in vivo Electroporation. The 23rd Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc), NOV. 2008.
Pirouz Daftarian, &and Don J. Diamond. Novel Epitope Peptide Fusions Conjugated with CpG ssODN Confer Enhanced Immunogenicity and HIV Recognition. Vaccine 2005; 23:3453-68.
Pirouz Daftarian, ..and Joshua D.I. Ellenhorn. Two Distinct Pathways of Immuno-modulation Improve Potency of p53 Immunization in Rejecting Established Tumors. Cancer Research, 2004, 64: 5407.
Pirouz Daftarian, ..and Don J. Diamond. Immunization with T H-CTL Fusion Peptide and CpG DNA in Transgenic HLA A2 Mice Induces Recognition of HIV-infected T Cells and Clears a Recombinant Vaccinia Virus Challenge. Journal of Immunology, 2003, 171(8).
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