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Molecular Pharmaceutics 2020-Apr

A DNA vaccine delivery platform based on Elastin-Like Recombinamer nanosystems for Rift Valley fever virus.

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Juan Gonzalez-Valdivieso
Belen Borrego
Alessandra Girotti
Sandra Moreno
Alejandro Brun
Jesus Bermejo-Martin
F Arias

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This work analyzes the immunogenicity of six genetically engineered constructs based on Elastin-Like Recombinamers (ELRs) fused to the Gn glycoprotein from Rift Valley fever virus (RVFV). Upon transfection, all constructs showed no effect on cell viability. While fusion constructs including ELR blocks containing hydrophobic amino acids (alanine or isoleucine) did not increase the expression of viral Gn in eukaryotic cells, glutamic acid- or valine-rich fusion proteins showed enhanced expression levels compared to the constructs encoding the viral antigen alone. However, in vivo DNA plasmid immunization assays determined that the more hydrophobic constructs reduced viremia levels after RVFV challenge to a higher extent that glutamic or valine-rich encoding plasmids and were better inducers of cellular immunity as judged by in vitro re-stimulation experiments. Although the Gn-ELR fusion constructs did not surpass the protective efficacy of a plasmid vaccine expressing non-fused Gn, our results warrant further experiments directed to take advantage of the immunomodulatory potential of ELR biomaterials for improving vaccines against infectious diseases.

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