%A Anurag Sankhyan
%A Chandresh Sharma
%A Durgashree Dutta
%A Tarang Sharma
%A Kunzang Chosdol
%A Takaji Wakita
%A Koichi Watashi
%A Amit Awasthi
%A Subrat K Acharya
%A Navin Khanna
%A Ashutosh Tiwari
%A Subrata Sinha
%O Open Access
%J Scientific reports
%T Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals.
%X 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.
%K Antibody therapy; Transnational immunology

%P 21240
%V 6
%D 2016
%I NPG
%L open1900