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

Autor: Steven W. Wingett, Kassim Kamaka, Danika L. Hill, Martin S. Zand, Jiong Wang, Elizabeth F. Wallin, Catherine Mkindi, François Spertini, Wim Pierson, Régine Audran, Daniel J. Bolland, Said Jongo, Sophie Houard, Michelle A. Linterman, Anne E. Corcoran, Edward J. Carr, Claudia Daubenberger
Přispěvatelé: Hill, Danika L [0000-0001-6284-7061], Carr, Edward [0000-0001-9343-4593], Corcoran, Anne Elizabeth [0000-0002-9577-5313], Linterman, Michelle [0000-0001-6047-1996], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
Receptors
Antigen
T-Cell
alpha-beta
Aluminum Hydroxide
Antibodies
Viral
Immunoglobulin G
0302 clinical medicine
Glucosides
Immunology and Allergy
Research Articles
Cells
Cultured
Aged
80 and over
education.field_of_study
B-Lymphocytes
Malaria vaccine
Vaccination
T-Lymphocytes
Helper-Inducer
Middle Aged
3. Good health
Lipid A
Influenza Vaccines
030220 oncology & carcinogenesis
Female
Adjuvant
Adult
Adolescent
Drug Compounding
Immunology
Population
Plasmodium falciparum
Antigens
Protozoan
Biology
Adjuvants
Immunologic/pharmacology
Aged
Aluminum Hydroxide/pharmacology
Antibodies
Viral/drug effects
Antibodies
Viral/immunology
Antigens
Protozoan/immunology
B-Lymphocytes/immunology
Drug Compounding/methods
Germinal Center/immunology
Glucosides/pharmacology
Humans
Immunity
Humoral/immunology
Influenza Vaccines/immunology
Lipid A/pharmacology
Lymph Nodes/immunology
Malaria Vaccines/immunology
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
Article
03 medical and health sciences
Antigen
Adjuvants
Immunologic
parasitic diseases
Malaria Vaccines
medicine
education
Germinal center
Germinal Center
Immunity
Humoral
030104 developmental biology
Humoral immunity
biology.protein
Lymph Nodes
Zdroj: The Journal of experimental medicine, vol. 216, no. 8, pp. 1857-1873
The Journal of Experimental Medicine
Popis: A rational strategy to achieve optimal vaccine responses is to potentiate Tfh cells and the germinal center response. This work shows the adjuvant GLA-SE enhances circulating Tfh cells and enduring antibody responses to a malaria vaccine in Tanzanian adults.
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.
Graphical Abstract
Databáze: OpenAIRE
Externí odkaz: