A DNA Vaccine That Encodes an Antigen-Presenting Cell-Specific Heterodimeric Protein Protects against Cancer and Influenza

Molecular Therapy. Methods & Clinical Development
Ranveig BraathenBjarne Bogen

Abstract

Immunogenicity of DNA vaccines can be increased by constructing the DNA in such a way that it encodes secreted homodimeric fusion proteins that target antigen-presenting cells (APCs). In this study, we have developed novel APC-targeting vaccine molecules with an increased flexibility due to introduction of a heterodimerization motif. The heterodimeric proteins permit four different fusions within a single molecule, thus allowing expression of two different APC-targeting moieties and two different antigens. Two types of heterodimeric fusion proteins were developed that employed either the ACID/BASE or the Barnase/Barstar motifs, respectively. The ACID/BASE heterodimeric vaccines conferred protection against challenges with either influenza virus or tumor cells in separate preclinical models. The ACID/BASE motif was flexible since a large number of different targeting moieties and antigens could be introduced with maintenance of specificity, antigenicity, and secretion. APC-targeting ACID/BASE vaccines expressing two different antigens induced antibody and T cell responses against either of the two antigens. Heterodimeric ACID/BASE DNA vaccines were of approximately the same potency as previously reported homodimeric DNA vaccines...Continue Reading

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Citations

Mar 12, 2021·Drug Delivery and Translational Research·Dongyoon KimYu-Kyoung Oh
Jan 16, 2021·ACS Biomaterials Science & Engineering·Jie WangHao Wang
Sep 29, 2021·Expert Review of Vaccines·Vivek P ChavdaVasso Apostolopoulos

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Methods Mentioned

BETA
ELISAs
ELISA
transfection
transfections
PCR
Assay

Software Mentioned

Magellan
GraphPad Prism
LivingImage

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