151. Immune history profoundly affects broadly protective B cell responses to influenza
- Author
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William Taylor, Peter Palese, Noel T. Pauli, Carole J. Henry Dunand, Sarah F. Andrews, Jane-Hwei Lee, Min Huang, Marlene Salgado-Ferrer, Rafi Ahmed, Kaval Kaur, Florian Krammer, Yunping Huang, Patrick C. Wilson, Lyubov I. Popova, Jens Wrammert, Irvin Y. Ho, Samuel Lim, and Xinyan Qu
- Subjects
Adult ,Male ,Influenza vaccine ,Molecular Sequence Data ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Immunodominance ,Cell Separation ,medicine.disease_cause ,Antibodies, Viral ,Epitope ,Article ,Madin Darby Canine Kidney Cells ,Epitopes ,Immune system ,Dogs ,Influenza A Virus, H1N1 Subtype ,Immunity ,Influenza, Human ,Influenza A virus ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Phylogeny ,B-Lymphocytes ,biology ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,Surface Plasmon Resonance ,Virology ,Antibodies, Neutralizing ,Influenza Vaccines ,Immunology ,biology.protein ,Leukocytes, Mononuclear ,Female ,Antibody - Abstract
Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years. Analysis of monoclonal antibodies generated from vaccine-induced plasmablasts demonstrated that individuals with low preexisting serological titers to the vaccinating strain generated a broadly reactive, hemagglutinin (HA) stalk-biased response. Higher preexisting serum antibody levels correlated with a strain-specific HA head-dominated response. We demonstrate that this HA head immunodominance encompasses poor accessibility of the HA stalk epitopes. Further, we show polyreactivity of HA stalk-reactive antibodies that could cause counterselection of these cells. Thus, preexisting memory B cells against HA head epitopes predominate, inhibiting a broadly protective response against the HA stalk upon revaccination with similar strains. Consideration of influenza exposure history is critical for new vaccine strategies designed to elicit broadly neutralizing antibodies.
- Published
- 2015