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Sankhyan, A and Sharma, C and Dutta, D and Sharma, T and Chosdol, K and Wakita, T and Watashi, K and Awasthi, A and Acharya, SK and Khanna, N and Tiwari, A and Sinha, S (2016) Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals. Scientific Reports, 6. p. 21240.

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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.

Item Type: Article
Subjects: Neuro-Oncological Disorders
Genetics and Molecular Biology
Depositing User: Dr. D.D. Lal
Date Deposited: 04 May 2017 05:42
Last Modified: 02 Jan 2018 09:28
URI: http://nbrc.sciencecentral.in/id/eprint/36

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