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Sci Immunol. 2019 Apr 19;4(34). pii: eaau2710. doi: 10.1126/sciimmunol.aau2710.

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

Author information

1
HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
2
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
3
Department of Biochemistry and Molecular Biophysics, Zukerman Institute of Mind Brain Behavior, Columbia University, New York, NY 10032, USA.
4
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
6
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
7
Emergent Biosolutions Inc., Gaithersburg, MD 20879, USA.
8
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Admnistration, Silver Spring, MD 20993, USA.
9
HIV-Specific Immunity Section of the Laboratory of Immunoregulation, National Institutes of Health (NIH), Bethesda, MD 20892, USA. mconnors@nih.gov.

Abstract

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.

PMID:
31004012
DOI:
10.1126/sciimmunol.aau2710

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