Immune history profoundly affects broadly protective B cell responses to influenza
| Autor: | 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, Xinyan Qu |
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| Rok vydání: | 2015 |
| Předmět: |
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 |
| Zdroj: | Science translational medicine. 7(316) |
| ISSN: | 1946-6242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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