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

J Exp Med. 2019 Aug 5;216(8):1857-1873. doi: 10.1084/jem.20190301. Epub 2019 Jun 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, Protozoan
  • Glucosides
  • Influenza Vaccines
  • Lipid A
  • Malaria Vaccines
  • Receptors, Antigen, T-Cell, alpha-beta
  • glucopyranosyl lipid-A
  • Aluminum Hydroxide