Llama-derived single-domain intrabodies inhibit secretion of hepatitis B virions in mice.
Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single-domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics-based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10- to >100-fold reduction in the concentration of HBV virions in plasma.


CONCLUSIONS
VHHs potently inhibited secretion of HBV virions in vivo, showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody-mediated inhibition of viral secretion in mammals.
Serruys
Benedikte
B
Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.
Van Houtte
Freya
F
Verbrugghe
Phebe
P
Leroux-Roels
Geert
G
Vanlandschoot
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions; D002161:Camelids, New World / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D045744:Cell Line, Tumor; D006514:Hepatitis B Surface Antigens / Q000187:drug effects / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000187:drug effects / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D014162:Transfection; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*; D014771:Virion; D014779:Virus Replication / Q000187:drug effects
D000906:Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D019151:Peptide Library; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins