Longitudinal Dynamics of the Human B Cell Response to the Yellow Fever 17D Vaccine – March 9, 2020

PNAS March 9, 2020 https://doi.org/10.1073/pnas.1921388117

Anna Z. Wec, Denise Haslwanter, Yasmina N. Abdiche, Laila Shehata, Nuria Pedreno-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, Felix A. Rey, Giovanna Barba-Spaeth, Kartik Chandran, and Laura M. Walker

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.