Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 181, Issue 12, Pages 1407-1417Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200910-1484OC
Keywords
tuberculosis; vaccine; immunity; CD4; CD8
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Funding
- Aeras Global Tuberculosis Vaccine Foundation
- Crucell NV
- NRF
- NIH [RO1-AI065653, NO1-AI70022]
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Rationale: AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guerin (BCG), the only licensed vaccine. Objectives: We investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa. Methods: 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. Measurements and Main Results: 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 IFNI-gamma and/or tumor necrosis factor-alpha, which persisted for the duration of the study. Conclusions: 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.
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