Abstract
A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+ and atypical IgM+ and IgD+ MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.
Original language | English (US) |
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Pages (from-to) | 6675-6685 |
Number of pages | 11 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 117 |
Issue number | 12 |
DOIs | |
State | Published - Mar 24 2020 |
Keywords
- Antibody responses
- Antiviral vaccination
- B cell memory
- Monoclonal antibody
- Yellow fever virus
ASJC Scopus subject areas
- General