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

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. The flexibility and potency of the ACID/BASE format suggest that it could be a useful platform for DNA vaccines that encode APC-targeting fusion proteins.

DNA vaccines for SARS-CoV-2: toward third-generation vaccination era

“…They are administered via intramuscular, subcutaneous, mucosal, or transdermal routes ( Figure 2 ) [ 57 ]. Myocytes and antigen-presenting cells are the primary targets of DNA vaccine [ 58 ]. Here, the plasmid encoding the antigen of interest is delivered into the host cell’s nucleus, where they undergo transcription and translation process with the help of host cell machinery ( Figure 2 ).…”

Barnase-Barstar Pair: Contemporary Application in Cancer Research and Nanotechnology

“…The use of barnase-barstar modules fused to 4D5scFv made it possible to assemble di-and trimeric complexes with increased avidity and molecular weight (81 kDa and 132 kDa versus 30 kDa of 4D5scFv monomer) [9]. Barnase and barstar were used as heterodimerising modules in a novel anticancer DNA vaccine [65,66], bringing together two units composed of an antigen presenting a cell targeting motif and an immunogenic motif. In combination with the easy cloning strategy, the heterodimeric barnase-barstar vaccine molecule provided a flexible platform for development of novel DNA vaccines [66].…”

Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

“…MOPC315.BM has provided additional insights into myeloma immunology. Examples include the interaction of myeloid-derived suppressor cells and T cells in vivo ( 120 ), the development of allogeneic T cell treatments for myeloma that may circumvent GvHD ( 121 , 122 ), and the evaluation of novel DNA vaccines for immunotherapeutic purposes ( 123 ). Similar to the inconvenience of the genetic background of 5TMM, MOPC315.BM is on the genetic background of BALB/c (C), which is not as widely used in cancer immunology as B6.…”