The Novel TB Vaccine, AERAS-402, Induces Robust and Pulyfunctional CD4 and CD8 T Cells in Adults
- Department for International Development
- South Africa
- Document Type:
- Journal Article
- 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., and Weverling, G.J.
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).
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]
Country: South Africa
Document Type: Journal Article
Authors: 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.