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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Induction and regulation of T-cell immunity by the novel tuberculosis vaccine M72/AS01 in South African adults
American Journal of Respiratory and Critical Care Medicine, Volume 188, No. 4, Year 2013
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Description
Rationale: Tuberculosis (TB) is a major cause of morbidity and mortality worldwide, thus there is an urgent need for novel TB vaccines. Objectives: We investigated a novel TB vaccine candidate, M72/ AS01, in a phase IIa trial of bacille Calmette-Gue rin-vaccinated, HIV-uninfected, and Mycobacterium tuberculosis (Mtb)-infected and -uninfected adults in South Africa. Methods: Two doses of M72/AS01 were administered to healthy adults, with and without latent Mtb infection. Participants were monitored for 7 months after the first dose; cytokine production profiles, cell cycling, and regulatory phenotypes of vaccine-induced T cells were measured by flow cytometry. Measurements and Main Results: The vaccine had a clinically acceptable safety profile, and induced robust, long-lived M72-specific T-cell and antibody responses. M72-specific CD4 T cells produced multiple combinations of Th1 cytokines. Analysis of T-cell Ki67 expression showed that most vaccination-induced T cells did not express Th1 cytokines or IL-17; these cytokine-negative Ki671 T cells included subsets of CD4 T cells with regulatory phenotypes. PD-1, a negative regulator of activatedTcells,wastransiently expressedon M72-specific CD4 T cells after vaccination. Specific T-cell subsets were present at significantly higher frequencies after vaccination of Mtb-infected versus -uninfected participants. Conclusions: M72/AS01 is clinically well tolerated in Mtb-infected and -uninfected adults, induces high frequencies of multifunctional T cells, and boosts distinct T-cell responses primed by natural Mtb infection. Moreover, these results provide important novel insights into how this immunity may be appropriately regulated after novel TB vaccination of Mtb-infected and -uninfected individuals. Copyright © 2013 by the American Thoracic Society.
Authors & Co-Authors
Day, Cheryl Cheryl L.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
United States, Atlanta
Rollins School of Public Health
United States, Atlanta
Emory University
Tameris, Michele D.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Mansoor, Nazma
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
van Rooyen, Michele
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
de Kock, Marwou
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Geldenhuys, Hennie D.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Erasmus, Mzwandile
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Makhethe, Lebohang
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Hughes, Elizabeth Jane
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Gelderbloem, Sebastian J.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
South Africa, Observatory
Aeras Africa
Bollaerts, Anne
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Bourguignon, Patricia
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Cohen, Joe D.
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Demoitié, Marie Ange
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Mettens, Pascal
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Moris, Philippe J.
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Sadoff, Jerald C.
United States, Rockville
Aeras Global tb Vaccine Foundation
Netherlands, Leiden
Crucell nv
Hawkridge, Anthony J.
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Hussey, Greg Dudley
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Mahomed, Hassan
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Ofori-Anyinam, Opokua
Belgium, Wavre
Glaxosmithkline Pharmaceuticals Sa/nv
Hanekom, Willem Albert
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Statistics
Citations: 105
Authors: 22
Affiliations: 7
Identifiers
Doi:
10.1164/rccm.201208-1385OC
ISSN:
1073449X
Research Areas
Infectious Diseases
Study Locations
South Africa