Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.
Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non-neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines.
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Carole J
CJ
Henry Dunand
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Paul E
PE
Leon
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Min
M
Huang
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Angela
A
Choi
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Veronika
V
Chromikova
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Irvin Y
IY
Ho
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Gene S
GS
Tan
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
John
J
Cruz
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ariana
A
Hirsh
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA.
Nai-Ying
NY
Zheng
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Caitlin E
CE
Mullarkey
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Francis A
FA
Ennis
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Masanori
M
Terajima
Division of Infectious Disease, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
John J
JJ
Treanor
Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
David J
DJ
Topham
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20852, USA.
Kanta
K
Subbarao
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Peter
P
Palese
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@mssm.edu.
Florian
F
Krammer
The Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA. Electronic address: wilsonp@uchicago.edu.
Patrick C
PC
Wilson
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines