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Receptor Mimicry by Human Antibody F045–092 Inhibits Influenza H3N2
Author(s) -
Considine Camille,
Palakodeti Samhita,
Handmacher Matt,
Sagart Arman,
Eherenfeldt Hannah,
Moerder Susan,
Lee Peter
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb189
Subject(s) - avidity , antibody , virology , molecular mimicry , receptor , neutralizing antibody , hemagglutinin (influenza) , neutralization , glycoprotein , antibody dependent enhancement , biology , sialic acid , viral entry , virus , immunology , microbiology and biotechnology , viral replication , genetics
According to the CDC, influenza is the 9th leading cause of death in the US, killing over 50,000 people in 2011. H3N2, an influenza A serotype, is important for current research due to its increasing circulation in humans this season. To combat infections, flu vaccines are administered each year; however, due to continual mutations of the viral proteins, a vaccine offers little protection if the match between it and the dominant circulating strain is poor. Hemagglutinin (HA), the major glycoprotein on the viral surface, binds to host cell sialic acid receptors and initiates viral infection; thus blocking this viral‐host interaction prevents infection. F045–092, a broadly‐neutralizing antibody, targets the receptor binding site of HA and uses remarkable receptor mimicry to recognize all H3 strains from 1968 to 2011. The antibody binds primarily through a long HCDR3 loop that inserts into the HA receptor binding pocket. In addition, the antibody extends its breadth of neutralization using avidity, as the bivalent IgG has higher apparent affinity than the monovalent Fab. This broadly‐neutralizing antibody will potentially enable and inform the development of a pan‐H3 vaccine and small molecule therapeutics. Using 3D printing technology, the Francis Parker SMART (Students Modeling A Research Topic) Team modeled the antibody F045–092 in complex with HA. Supported by a grant from TSRI and UCSD.