Quantitative, molecular-level analysis of the serum antibody repertoire reveals unanticipated features of the response to seasonal influenza vaccination
June 12-17, 2016
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.
Jiwon Lee, Daniel R. Boutz, M. Gordon Joyce, Christopher Vollmers, Kwanyee Leung, Andrew P. Horton, Brandon J. DeKosky, Chang-Han Lee, Jason J. Lavinder, Kam Hon Hoi, Yaroslav Tsybovsky, Wing-Pui Kong, Daechan Park, Veronika Chromikova, Ted M. Ross, Andrew D. Ellington, Edward M. Marcotte, John R. Mascola, Florian Krammer, Gregory C. Ippolito, Stephen R. Quake, Peter D. Kwong, and George Georgiou, "Quantitative, molecular-level analysis of the serum antibody repertoire reveals unanticipated features of the response to seasonal influenza vaccination" in "Vaccine Technology VI", Laura Palomares, UNAM, Mexico Manon Cox, Protein Sciences Corporation, USA Tarit Mukhopadhyay, University College London, UK Nathalie Garçon, BIOASTER Technology Research Institute, FR Eds, ECI Symposium Series, (2016). http://dc.engconfintl.org/vaccine_vi/6