Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine
Anna Z. Wec, Denise Haslwanter, Yasmina Abdiche, Laila Shehata, Núria Pedreño-López, Crystal L. Moyer, Zachary A. Bornholdt, Asparouh Lilov, Juergen H. Nett, Rohit K. Jangra, Michael E. Brown, David I. Watkins, Clas Ahlm, Mattias N.E. Forsell, F.A. Rey, Giovanna Barba–Spaeth, Kartik Chandran, 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.