Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 42, Pages 17040-17045Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1212371109
Keywords
-
Categories
Funding
- Skaggs Institute of Chemical Biology
- National Institutes of Health Molecular Evolution Training Program [GM080209]
- Japan Science and Technology Agency Basic Research Programs
- Japan Initiative for Global Research Network on Infections Diseases
- Ministry of Education, Culture, Sports, Science, and Technology
- National Cancer Institute [Y1-CO-1020]
- National Institute of General Medical Sciences [Y1-GM-1104]
- US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]
- [AI058113]
- Grants-in-Aid for Scientific Research [24390110, 24658252] Funding Source: KAKEN
Ask authors/readers for more resources
Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes.
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