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 Yang; M 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

doi:10.1126/sciimmunol.aau2710

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

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

Authors

Kenta Matsuda¹, Jinghe Huang¹, Tongqing Zhou², Zizhang Sheng³, Byong H Kang¹, Elise Ishida¹, Trevor Griesman¹, Sarah Stuccio¹, Lyuba Bolkhovitinov¹, Teddy J Wohlbold⁴, Veronika Chromikova⁴, Alberto Cagigi², Kwanyee Leung², Sarah Andrews², Crystal S F Cheung², Alyssa A Pullano¹, Jason Plyler², Cinque Soto², Baoshan Zhang², Yongping Yang², M Gordon Joyce², Yaroslav Tsybovsky⁵, Adam Wheatley², Sandeep R Narpala², Yicheng Guo³, Sam Darko², Robert T Bailer², April Poole¹, C Jason Liang⁶, Jon Smith⁷, Jeff Alexander⁷, Marc Gurwith⁷, Stephen A Migueles¹, Richard A Koup², Hana Golding⁸, Surender Khurana⁸, Adrian B McDermott², Lawrence Shapiro³, Florian Krammer⁴, Peter D Kwong², Mark Connors⁹

Affiliations

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. [email protected].

PMID: 31004012
DOI: 10.1126/sciimmunol.aau2710

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.

Publication types

Clinical Trial, Phase I
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenoviridae / genetics*
Adenoviridae / immunology
Administration, Oral
Adolescent
Adult
Antibodies, Viral / blood
Antibodies, Viral / genetics
Antibodies, Viral / immunology
B-Lymphocytes / immunology*
Female
Genetic Vectors / genetics
Genetic Vectors / immunology
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Humans
Immunogenicity, Vaccine
Influenza A Virus, H5N1 Subtype / genetics
Influenza A Virus, H5N1 Subtype / immunology*
Influenza Vaccines / administration & dosage
Influenza Vaccines / adverse effects
Influenza Vaccines / genetics
Influenza Vaccines / immunology*
Influenza, Human / immunology
Influenza, Human / prevention & control*
Influenza, Human / virology
Male
Middle Aged
Somatic Hypermutation, Immunoglobulin / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / adverse effects
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Virus Replication / immunology
Young Adult

Substances

Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
Vaccines, Synthetic
hemagglutinin, avian influenza A virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding