UNLABELLED: 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. CONCLUSION: 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.
UNLABELLED: 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 infectedpatients 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 HBVmouse 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. CONCLUSION: 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.
Authors: Andrew S Dixon; Jonathan E Constance; Tomoyuki Tanaka; Terence H Rabbitts; Carol S Lim Journal: Pharm Res Date: 2011-12-20 Impact factor: 4.200
Authors: Anna Hultberg; Nigel J Temperton; Valérie Rosseels; Mireille Koenders; Maria Gonzalez-Pajuelo; Bert Schepens; Lorena Itatí Ibañez; Peter Vanlandschoot; Joris Schillemans; Michael Saunders; Robin A Weiss; Xavier Saelens; José A Melero; C Theo Verrips; Steven Van Gucht; Hans J de Haard Journal: PLoS One Date: 2011-04-01 Impact factor: 3.240
Authors: Janusz Wesolowski; Vanina Alzogaray; Jan Reyelt; Mandy Unger; Karla Juarez; Mariela Urrutia; Ana Cauerhff; Welbeck Danquah; Björn Rissiek; Felix Scheuplein; Nicole Schwarz; Sahil Adriouch; Olivier Boyer; Michel Seman; Alexei Licea; David V Serreze; Fernando A Goldbaum; Friedrich Haag; Friedrich Koch-Nolte Journal: Med Microbiol Immunol Date: 2009-06-16 Impact factor: 3.402