Title

Quantitative, molecular-level analysis of the serum antibody repertoire reveals unanticipated features of the response to seasonal influenza vaccination

Authors

Jiwon Lee, Depart. of Chemical Engineering, University of Texas at Austin, AustinFollow
Daniel R. Boutz, Center of Systems and Synthetic Biology, University of Texas at Austin, Austin
M. Gordon Joyce, Vaccine Research Center, National Institutes of Health, Bethesda
Christopher Vollmers, Depart. of Bioengineering and Applied Physics, Stanford University, Stanford
Kwanyee Leung, Vaccine Research Center, National Institutes of Health, Bethesda
Andrew P. Horton, Center of Systems and Synthetic Biology, University of Texas at Austin, Austin
Brandon J. DeKosky, Vaccine Research Center, National Institutes of Health, Bethesda
Chang-Han Lee, Depart. of Chemical Engineering, University of Texas at Austin, Austin
Jason J. Lavinder, Depart. of Chemical Engineering, University of Texas at Austin, Austin
Kam Hon Hoi, Antibody Engineering Department, Genentech Inc, South San Francisco
Yaroslav Tsybovsky, Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick
Wing-Pui Kong, Vaccine Research Center, National Institutes of Health, Bethesda
Daechan Park, Depart. of Chemical Engineering, University of Texas at Austin, Austin
Veronika Chromikova, Depart. of Microbiology, Icahn School of Medicine at Mount Sinai, New York
Ted M. Ross, Depart. of Infectious Diseases, University of Georgia, Athens
Andrew D. Ellington, Center of Systems and Synthetic Biology, University of Texas at Austin, Austin
Edward M. Marcotte, Center of Systems and Synthetic Biology, University of Texas at Austin, Austin
John R. Mascola, Vaccine Research Center, National Institutes of Health, Bethesda
Florian Krammer, Depart. of Microbiology, Icahn School of Medicine at Mount Sinai, New York
Gregory C. Ippolito, Depart. of Molecular Biosciences, University of Texas at Austin, Austin
Stephen R. Quake, Depart. of Bioengineering and Applied Physics, Stanford University
Peter D. Kwong, Vaccine Research Center, National Institutes of Health, Bethesda
George Georgiou, Depart. of Chemical Engineering, University of Texas at Austin, Austin

Conference Dates

June 12-17, 2016

Abstract

Vaccines convey protection by stimulating B cells to produce a diverse repertoire of antigen-specific antibody proteins for an extended period of time. While antibodies in circulation following vaccination are critical for protection to influenza infection, the identities and biochemical properties of the individual antibodies that constitute the polyclonal serum response remain unknown. Here, we used recently developed techniques to directly analyze the composition of four human donors’ serum antibody repertoires to each of the three monovalent strains in the 2011-2012 seasonal trivalent inactivated vaccine. A time-course analysis reveals that >60% of the post-vaccination serum response comprised of antibodies which pre-existed in sera prior to the vaccination that became boosted. Our data also show unexpected prevalence (>30%) of antibodies cross-reactive between H1 and H3 in sera. Characterization of recombinant antibodies led to a discovery of a novel class of broadly cross-reactive, but non-neutralizing antibodies. These antibodies displayed exceptional binding breadth to group 1 and group 2 hemagglutinins by recognizing a newly-identified conserved epitope in the head domain that is exposed only in monomeric form of the hemagglutinins. These antibodies conferred protection in lethal challenge mice models. Additionally, we identified a group of stem-binding antibodies with broad binding and neutralization in pseudo-virus neutralization assays. Some of these antibodies were abundant in serum. This is the first-ever report providing an extensive molecular-level description of the human serum antibody response to seasonal flu vaccination, and collectively, this data provide unprecedented insights on the serological response to influenza vaccination that have direct implication for the design of immunogens for a future universal flu vaccine.

Additional Files
Jiwon Lee - 5.pdf (181 kB)

This document is currently not available here.

Share

COinS