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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08

AUTHORS

Anurag Sankhyan, Chandresh Sharma, Durgashree Dutta, Tarang Sharma, Kunzang Chosdol, Takaji Wakita, Koichi Watashi, Amit Awasthi, Subrat K Acharya, Navin Khanna, Ashutosh Tiwari, Subrata Sinha

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. More... »

PAGES

21240

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep21240

DOI

http://dx.doi.org/10.1038/srep21240

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000382480

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26888694


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