Insertion of a targeting peptide on capsid surface loops of human papillomavirus type-16 virus-like particles mediate elimination of anti-dsDNA Abs-producing B cells with high efficiency.
The purpose of this study was to design chimeric human papillomavirus type-16 L1 virus-like particles (VLPs) and to explore the potential capacity of elimination to anti-dsDNA antibody-producing B cells. To test it, VLPs were achieved by combination of human papillomavirus type-16 L1 proteins inserted into a targeting peptide (DWEYSVWLSN) and plasmids encoding diphtheria toxin A ligand. Additionally, VLPs were cocultured with target cells to assess the killing efficiency by lactate dehydrogenase assay in vitro. Lastly, lupus-prone (BWF1) mice vaccinated with VLPs were used as a model to assess the killing efficiency in vivo. The results showed that the VLPs were constructed successfully, and possessed the potential of killing anti-dsDNA antibody-producing B cells with high efficiency. The findings indicate the possibility that the VLPs ablate autoreactive B cells represents a novel strategy in the immunotherapy of autoantibody-mediated diseases.
Wang
Huiming
H
Renal Department, Third Military Medical University, Chongqing, PR China.
Yang
Zhao
Z
Li
Fan
F
He
Yani
Y
Wang
Shuguang
S
Yang
Di
D
Wu
Yuzhang
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D036022:Capsid Proteins / Q000276:immunology* / Q000378:metabolism; D004167:Diphtheria Toxin / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D036022:Capsid Proteins; D004167:Diphtheria Toxin; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C029795:diphtheria toxin fragment A; C063317:L1 protein, Human papillomavirus type 16