Journal
JOURNAL OF VIROLOGY
Volume 86, Issue 6, Pages 2978-2989Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.06665-11
Keywords
-
Categories
Funding
- French Ministry of Health
- Chinese National Science Foundation [30671922]
- National Science and Technology Major Projects [2008ZX10001-010, 2009ZX10004-105, 2009ZX10004-016]
- Li Kai-Shing Foundation of Hong Kong
- United Kingdom Medical Research Council
- MRC [G0600522, MC_U117584222] Funding Source: UKRI
- Medical Research Council [G0600522, MC_U117584222] Funding Source: researchfish
Ask authors/readers for more resources
Influenza A virus infection is a persistent threat to public health worldwide due to its ability to evade immune surveillance through rapid genetic drift and shift. Current vaccines against influenza A virus provide immunity to viral isolates that are similar to vaccine strains. High-affinity neutralizing antibodies against conserved epitopes could provide immunity to diverse influenza virus strains and protection against future pandemic viruses. In this study, by using a highly sensitive H5N1 pseudotype-based neutralization assay to screen human monoclonal antibodies produced by memory B cells from an H5N1-infected individual and molecular cloning techniques, we developed three fully human monoclonal antibodies. Among them, antibody 65C6 exhibited potent neutralization activity against all H5 clades and subclades except for subclade 7.2 and prophylactic and therapeutic efficacy against highly pathogenic avian influenza H5N1 viruses in mice. Studies on hemagglutinin (HA)-antibody complexes by electron microscopy and epitope mapping indicate that antibody 65C6 binds to a conformational epitope comprising amino acid residues at positions 118, 121, 161, 164, and 167 (according to mature H5 numbering) on the tip of the membrane-distal globular domain of HA. Thus, we conclude that antibody 65C6 recognizes a neutralization epitope in the globular head of HA that is conserved among almost all divergent H5N1 influenza stains.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available