The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B9B6A1FE4844
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes.
Journal
The Journal of experimental medicine
Author(s)
Hill D.L., Pierson W., Bolland D.J., Mkindi C., Carr E.J., Wang J., Houard S., Wingett S.W., Audran R., Wallin E.F., Jongo S.A., Kamaka K., Zand M., Spertini F., Daubenberger C., Corcoran A.E., Linterman M.A.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
05/08/2019
Peer-reviewed
Oui
Volume
216
Number
8
Pages
1857-1873
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite the central role of Tfh cells in vaccine responses, there is currently no validated way to enhance their differentiation in humans. From paired human lymph node and blood samples, we identify a population of circulating Tfh cells that are transcriptionally and clonally similar to germinal center Tfh cells. In a clinical trial of vaccine formulations, circulating Tfh cells were expanded in Tanzanian volunteers when an experimental malaria vaccine was adjuvanted in GLA-SE but not when formulated in Alum. The GLA-SE-formulated peptide was associated with an increase in the extrafollicular antibody response, long-lived antibody production, and the emergence of public TCRβ clonotypes in circulating Tfh cells. We demonstrate that altering vaccine adjuvants is a rational approach for enhancing Tfh cells in humans, thereby supporting the long-lived humoral immunity that is required for effective vaccines.
Keywords
Adjuvants, Immunologic/pharmacology, Adolescent, Adult, Aged, Aged, 80 and over, Aluminum Hydroxide/pharmacology, Antibodies, Viral/drug effects, Antibodies, Viral/immunology, Antigens, Protozoan/immunology, B-Lymphocytes/immunology, Cells, Cultured, Drug Compounding/methods, Female, Germinal Center/immunology, Glucosides/pharmacology, Humans, Immunity, Humoral/immunology, Influenza Vaccines/immunology, Lipid A/pharmacology, Lymph Nodes/immunology, Malaria Vaccines/immunology, Male, Middle Aged, Plasmodium falciparum/immunology, Receptors, Antigen, T-Cell, alpha-beta/genetics, Receptors, Antigen, T-Cell, alpha-beta/metabolism, T-Lymphocytes, Helper-Inducer/immunology, Vaccination/methods, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
17/06/2019 9:24
Last modification date
07/07/2020 5:20
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