EXPRESSION OF HBSAG VARIANTS TO IMPROVE THE EFFICACY OF THE CURRENT ANTI- HEPATITIS B VACCINE

PRISCILA PERAZZO; SORDELLI ANDREA; NICOLAS RODRIGUEZ; GALLEGO R; MOLINA R; SAQUIN J; B.C. NUDEL; GONZALEZ RH; A. D. NUSBLAT; MARIA LUJAN CUESTAS

Mar del Plata

Congreso; LI Reunion Anual 2015; 2015

Sociedad Argentina de Investigacion Bioquimica y Biologia Molecular

Introduction: Cocirculation of HBsAg and neutralizing anti-HBs antibodies in patients withadequate active/passive immunization or during the natural course of infection is a problem of health concern. The most widely reported S-escape mutants are D144A, G145R and those at cysteines. All anti-HBV vaccines available are only composed of wild-type (wt) HBsAg; the S-escape mutants described to date in the world are not included. Some of them may also escape immune detection by some commercial kits used in the diagnosis of HBV infection and in the screenings of blood donors.Aims: To analyze the effect of S mutants at various positions (eg,C107R,D144A,G145R) in relation to the interaction with anti-HBs antibodies from wt strains.Methods: Wt and mutant S genes were cloned into the expression vector pPICZa and transformed into Pichia pastoris X-33. For detection of HBsAg, commercial ELISA assays were performed. VLPs were characterized and reactivity of wt and mutant HBsAg was assayed in vitro (TEM and DLS) and in silico.Results: High expression levels were obtained, and the resulting VLPs had a size of about 20 nm. Reactivity with anti-HBs antibodies was variable.Conclusions: This may lead to the development of a new anti-HBV vaccine covering such escape mutants, as well as for the development of diagnostic tools needed - and still not available, for their detection, as some of them may escape their detection.