The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes
| العنوان: | The adjuvant GLA-SE promotes human Tfh cell expansion and emergence of public TCRβ clonotypes |
|---|---|
| المؤلفون: | 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 |
| المساهمون: | 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 |
| المصدر: | The Journal of experimental medicine, vol. 216, no. 8, pp. 1857-1873 The Journal of Experimental Medicine |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c02643e911e2eb9a88542a1b440cd038 https://serval.unil.ch/notice/serval:BIB_B9B6A1FE4844 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c02643e911e2eb9a88542a1b440cd038 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |