Prolonged evolution of the memory B cell response induced by a replicating adenovirus-influenza H5 vaccine

Kenta Matsuda, Jinghe Huang, Tongqing Zhou, Zizhang Sheng, Byong H. Kang, Elise Ishida, Trevor Griesman, Sarah Stuccio, Lyuba Bolkhovitinov, Teddy J. Wohlbold, Veronika Chromikova, Alberto Cagigi, Kwanyee Leung, Sarah Andrews, Crystal S.F. Cheung, Alyssa A. Pullano, Jason Plyler, Cinque Soto, Baoshan Zhang, Yongping YangM. Gordon Joyce, Yaroslav Tsybovsky, Adam Wheatley, Sandeep R. Narpala, Yicheng Guo, Sam Darko, Robert T. Bailer, April Poole, C. Jason Liang, Jon Smith, Jeff Alexander, Marc Gurwith, Stephen A. Migueles, Richard A. Koup, Hana Golding, Surender Khurana, Adrian B. McDermott, Lawrence Shapiro, Florian Krammer, Peter D. Kwong, Mark Connors

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34 Scopus citations


Induction of an antibody response capable of recognizing highly diverse strains is a major obstacle to the development of vaccines for viruses such as HIV and influenza. Here, we report the dynamics of B cell expansion and evolution at the single-cell level after vaccination with a replication-competent adenovirus type 4 recombinant virus expressing influenza H5 hemagglutinin. Fluorescent H1 or H5 probes were used to quantitate and isolate peripheral blood B cells and their antigen receptors. We observed increases in H5-specific antibody somatic hypermutation and potency for several months beyond the period of active viral replication that was not detectable at the serum level. Individual broad and potent antibodies could be isolated, including one stem-specific antibody that is part of a new multidonor class. These results demonstrate prolonged evolution of the B cell response for months after vaccination and should be considered in efforts to evaluate or boost vaccine-induced immunity.

Original languageEnglish
Article numbereaau2710
JournalScience immunology
Issue number34
StatePublished - 19 Apr 2019


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