Format

Send to

Choose Destination
Science. 2018 Nov 2;362(6414):598-602. doi: 10.1126/science.aaq0620.

Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
Janssen Research and Development, Spring House, PA 19002, USA.
3
Janssen Vaccines and Prevention, Archimedesweg 4-6, 2333 CN, Leiden, Netherlands.
4
Janssen Prevention Center, Archimedesweg 6, 2333 CN, Leiden, Netherlands.
5
Quantitative Sciences, Janssen Pharmaceutical Companies of Johnson and Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
6
Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
7
Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Janssen Infectious Diseases, Turnhoutseweg 30, 2340, Beerse, Belgium. wilson@scripps.edu jkolkman@its.jnj.com.
9
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. wilson@scripps.edu jkolkman@its.jnj.com.
10
Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.

PMID:
30385580
DOI:
10.1126/science.aaq0620

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center