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