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

Published version
Peer-reviewed

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Type

Article

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Authors

Pierson, Wim 
Bolland, Daniel J 
Mkindi, Catherine 
Carr, Edward J 

Abstract

jats:pThe 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.</jats:p>

Description

Keywords

Adjuvants, Immunologic, Adolescent, Adult, Aged, Aged, 80 and over, Aluminum Hydroxide, Antibodies, Viral, Antigens, Protozoan, B-Lymphocytes, Cells, Cultured, Drug Compounding, Female, Germinal Center, Glucosides, Humans, Immunity, Humoral, Influenza Vaccines, Lipid A, Lymph Nodes, Malaria Vaccines, Male, Middle Aged, Plasmodium falciparum, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Helper-Inducer, Vaccination, Young Adult

Journal Title

The Journal of Experimental Medicine

Conference Name

Journal ISSN

0022-1007
1540-9538

Volume Title

216

Publisher

Rockefeller University Press
Sponsorship
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)