title: Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals.
abstract: Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21-47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21-47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.|Center for Bio-design, and Diagnostics Translational Health Science and Technology Institute, Faridabad, Haryana, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Sankhyan
authors.affiliation: Center for Bio-design, and Diagnostics Translational Health Science and Technology Institute, Faridabad, Haryana, India.
authors.forename: Chandresh
authors.initials: C
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Durgashree
authors.initials: D
authors.lastname: Dutta
authors.affiliation: Center for Bio-design, and Diagnostics Translational Health Science and Technology Institute, Faridabad, Haryana, India.
authors.forename: Tarang
authors.initials: T
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Kunzang
authors.initials: K
authors.lastname: Chosdol
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.affiliation: Center for Human Microbial Ecology, Translational Health Science and Technology Institute, Faridabad, Haryana, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Subrat K
authors.initials: SK
authors.lastname: Acharya
authors.affiliation: Recombinant Gene Products Lab, International Center for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Navin
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Center for Bio-design, and Diagnostics Translational Health Science and Technology Institute, Faridabad, Haryana, India.|Experimental Medicine and Biotechnology Department, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tiwari
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.|National Brain Research Center, Manesar, Gurgaon, Haryana, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Sinha
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000276:immunology* / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; C050806:presurface protein 1, hepatitis B surface antigen