A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
Mice, Inbred BALB C
0303 health sciences
Antibodies, Monoclonal
Hemagglutinin Glycoproteins, Influenza Virus
CHO Cells
Article
Immunophenotyping
Madin Darby Canine Kidney Cells
3. Good health
03 medical and health sciences
Cricetulus
Dogs
Influenza A Virus, H1N1 Subtype
Influenza Vaccines
Cricetinae
Animals
Humans
Female
DOI:
10.1038/ncomms8708
Publication Date:
2015-07-21T15:18:50Z
AUTHORS (25)
ABSTRACT
AbstractEffective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.
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