tetano
Editor, Senior Moderator
Mol Ther Methods Clin Dev. 2020 Jan 25;17:378-392. doi: 10.1016/j.omtm.2020.01.007. eCollection 2020 Jun 12. [h=1]A DNA Vaccine That Encodes an Antigen-Presenting Cell-Specific Heterodimeric Protein Protects against Cancer and Influenza.[/h]
Braathen R[SUP]1[/SUP], Sp?ng HCL[SUP]1[/SUP], Hinke DM[SUP]1[/SUP], Blazevski J[SUP]1[/SUP], Bobic S[SUP]1[/SUP], Fossum E[SUP]1[/SUP], Bogen B[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
? 2020 The Author(s).
[h=4]KEYWORDS:[/h] APC targeting; DNA vaccine; heterodimer; influenza; myeloma
PMID: 32128342 PMCID: PMC7044496 DOI: 10.1016/j.omtm.2020.01.007
Free PMC Article
Braathen R[SUP]1[/SUP], Sp?ng HCL[SUP]1[/SUP], Hinke DM[SUP]1[/SUP], Blazevski J[SUP]1[/SUP], Bobic S[SUP]1[/SUP], Fossum E[SUP]1[/SUP], Bogen B[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
? 2020 The Author(s).
[h=4]KEYWORDS:[/h] APC targeting; DNA vaccine; heterodimer; influenza; myeloma
PMID: 32128342 PMCID: PMC7044496 DOI: 10.1016/j.omtm.2020.01.007
Free PMC Article