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

Abstract (Set) Various strategies have been developed for enhancing DNA vaccine potency by modifying the properties of Antigen Presenting Cells (APCs). These strategies include increasing the number of antigen-expressing Dendritic Cells (DCs); improving antigen expression, processing, and presentation in DCs; promoting DC activation and function; and enhancing DC and T cell interaction to augment vaccine-elicited T cell immune responses. JHU scientists have now developed a novel DNA vaccine encoding Ii-PADRE (Pan HLA-DR reactive epitope), a CD4+ T helper epitope, which enhance vaccine potency. C57BL/6 mice vaccinated with the novel DNA vaccine showed significantly greater PADRE-specific CD4+ T cell immune responses compared to control. In addition, co-administration of DNA encoding HPVE6 or E7 antigen and DNA encoding Ii-PADRE led to significantly stronger E6- or E7-specific immune responses and more potent protective and therapeutic antitumor effects against an E6/E7-expressing tumor model in mice compared to control. It appears that co-administration of DNA vaccines with Ii-PADRE DNA represents an effective approach for enhancing the generation of CD4+ T cells and eliciting stronger antigen-specific CD8+ T cell immune responses. Therefore, it is expected that this strategy may have significant potential for clinical translation. Description (Set) Proposed Use (Set) DNA vaccines have emerged as an important form of antigen-specific immunotherapy because of their safety, ease of production, and stability. However, DNA vaccines suffer from low immunogenicity. The potency of DNA vaccines can be enhanced by using particular methods to target DNA or encoded antigen to professional APCs and by modifying the properties of antigen-expressing APCs in order to boost vaccine-elicited immune responses. The current invention addresses the problem of low immunogenicity by employing a DNA vaccine encoding an Ii chain in which the CLIP region is replaced with PADRE (Ii-PADRE DNA). This invention enhances the potency of DNA vaccines and can be used to improve antigen-specific immune responses in many antigenic systems.

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