Phage Displayed HBV Core Antigen with Immunogenic Activity Aylin Ozdemir Bahadir & Bertan Koray Balcioglu & Kamil Serkan Uzyol & Ibrahim Hatipoglu & Ibrahim Sogut & Aynur Basalp & Berrin Erdag Received: 28 December 2010 / Accepted: 1 September 2011 / Published online: 14 September 2011 # Springer Science+Business Media, LLC 2011 Abstract Hepatitis B is a major public health problem worldwide, which may lead to chronic liver diseases such as cirrhosis and hepatocellular carcinoma. The hepatitis B core antigen (HBcAg) is one of the major viral proteins, which forms the inner core of hepatitis B virus (HBV) particles. In this study, filamentous bacteriophage M13 was genetically modified to display the polypeptides of HBcAg in order to develop an alternative carrier system. HBcAg gene was inserted into the minor coat protein (pIII) gene of M13, and HBcAg was expressed on the phage surface as a whole protein. Antigenicity and immunogenicity of HBcAg were tested by immunizing BALB/c mice three times with HBcAg-displaying recombinant phages. After successful immunization, one of the mice with high antibody titer to HBcAg was selected for fusion, and four monoclonal antibodies specific for HBcAg were developed. This result showed that HBcAg-displaying recombinant bacteriophages are immunogenic and can potentially be used for the development of monoclonal antibodies. Keywords HBcAg . Phage display . M13 phage . Immune response . ELISA . Monoclonal antibody Introduction Hepatitis B virus (HBV) infection, a major cause of human liver diseases, can lead to chronic liver diseases such as cirrhosis and hepatocellular carcinoma; it results in 620,000 annual deaths worldwide [1]. According to the World Health Organization (WHO) 2008 data, about 2 billion people worldwide have been infected with the virus and about 350 million live with chronic infection. Even though HBV infections can cause severe health Appl Biochem Biotechnol (2011) 165:1437–1447 DOI 10.1007/s12010-011-9365-1 A. O. Bahadir : B. K. Balcioglu : K. S. Uzyol : I. Hatipoglu : I. Sogut : A. Basalp : B. Erdag (*) Tubitak Marmara Research Center, Genetic Engineering and Biotechnology Institute, P.O. Box 21, 41470 Gebze, Kocaeli, Turkey e-mail: berrin.erdag@mam.gov.tr