Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals.

Sankhyan, Anurag and Sharma, Chandresh and Dutta, Durgashree and Sharma, Tarang and Chosdol, Kunzang and Wakita, Takaji and Watashi, Koichi and Awasthi, Amit and Acharya, Subrat K and Khanna, Navin and Tiwari, Ashutosh and Sinha, Subrata (2016) Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals. Scientific reports, 6. p. 21240. ISSN 2045-2322

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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
Additional Information:	Open Access
Uncontrolled Keywords:	Antibody therapy; Transnational immunology
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	29 Sep 2016 06:54
Last Modified:	29 Sep 2016 06:54
URI:	http://crdd.osdd.net/open/id/eprint/1900

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