Scientific Publication

The Novel TB Vaccine, AERAS-402, Induces Robust and Pulyfunctional CD4 and CD8 T Cells in Adults

author(s) Hughes, J.. - van der Merwe, L.. - Gearhart, J.. - Goudsmit, J.. - McClain, J.B.. - Pau, M.G.. - Sizemore, D.. - de Kock, M.. - Gelderbloem, S.. - Hanekom, W.A.. - Hatherill, M.. - Hawkridge, A.. - Hussey, G.D.. - Mahomed, H.. - Makhethe, L.. - Tameris, M.. - Veldsman, A.. - Sadoff, J.C.. - Erasmus, M.. - Mansoor, N.. - Abel, B.. - Abrahams, D.. - Goetz, M.. - Hendriks, J.. - Schirru, G.. - Weverling, G.J.
from UK Foreign, Commonwealth & Development Office (FCDO)
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themes
regions
  • Southern Africa
  • Sub-Saharan Africa
  • Africa
  • World
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Abel, B.; Tameris, M.; Mansoor, N.; Gelderbloem, S.; Hughes, J.; Abrahams, D.; Makhethe, L.; Erasmus, M.; de Kock, M.; van der Merwe, L.; Hawkridge, A.; Veldsman, A.; Hatherill, M.; Schirru, G.; Pau, M.G.; Hendriks, J.; Weverling, G.J.; Goudsmit, J.; Sizemore, D.; McClain, J.B.; Goetz, M.; Gearhart, J.; Mahomed, H.; Hussey, G.D.; Sadoff, J.C.; Hanekom, W.A. The Novel Tuberculosis Vaccine, AERAS-402, Induces Robust and Polyfunctional CD4+and CD8+T Cells in Adults. American Journal of Respiratory and Critical Care Medicine (2010) 181 (12) 1407-1417. (DOI: 10.1164/rccm.200910-1484OC)

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Abstract

AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine. The study investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa. Escalating doses of AERAS-402 vaccine were administered intramuscularly to each of three groups of healthy South African BCG-vaccinated adults, and a fourth group received two injections of the maximal dose. Participants were monitored for 6 months, with all adverse effects documented. Vaccine-induced CD4(+) and CD8(+) T-cell immunity was characterized by an intracellular cytokine staining assay of whole blood and peripheral blood mononuclear cells. AERAS-402 was well tolerated, and no vaccine-related serious adverse events were recorded. The vaccine induced a robust CD4(+) T-cell response dominated by cells coexpressing IFN-gamma, tumor necrosis factor-alpha, and IL-2 (\'polyfunctional\' cells). AERAS-402 also induced a potent CD8(+) T-cell response, characterized by cells expressing IFN-gamma and/or tumor necrosis factor-alpha, which persisted for the duration of the study. Vaccination with AERAS-402 is safe and immunogenic in healthy adults. The immunity induced by the vaccine appears promising: polyfunctional T cells are thought to be important for protection against intracellular pathogens such as Mycobacterium tuberculosis, and evidence is accumulating that CD8(+) T cells are also important. AERAS-402 induced a robust and durable CD8(+) T-cell response, which appears extremely promising. Clinical trial registered with www.sanctr.gov.za (NHREC no. 1381)

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