Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Anna Z. Wec, Denise Haslwanter, Yasmina N. Abdiche, Laila Shehata, Nuria Pedreño-Lopez, Crystal L. Moyer, Zachary A. Bornholdt, Asparouh Lilov, Juergen H. Nett, Rohit K. Jangra, Michael Brown, David I. Watkins, Clas Ahlm, Mattias N. Forsell, Félix A. Rey, Giovanna Barba-Spaeth, Kartik Chandran, Laura M. Walker

Research output: Contribution to journalArticle

1 Scopus citations

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 languageEnglish (US)
Pages (from-to)6675-6685
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number12
DOIs
StatePublished - Mar 24 2020

Keywords

  • Antibody responses
  • Antiviral vaccination
  • B cell memory
  • Monoclonal antibody
  • Yellow fever virus

ASJC Scopus subject areas

  • General

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  • Cite this

    Wec, A. Z., Haslwanter, D., Abdiche, Y. N., Shehata, L., Pedreño-Lopez, N., Moyer, C. L., Bornholdt, Z. A., Lilov, A., Nett, J. H., Jangra, R. K., Brown, M., Watkins, D. I., Ahlm, C., Forsell, M. N., Rey, F. A., Barba-Spaeth, G., Chandran, K., & Walker, L. M. (2020). Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine. Proceedings of the National Academy of Sciences of the United States of America, 117(12), 6675-6685. https://doi.org/10.1073/pnas.1921388117