Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa

被引：136

作者：

Hawkridge, Tony ^{[1
,2
]}

Scriba, Thomas J. ^{[1
,2
]}

Gelderbloem, Sebastian ^{[1
,2
]}

Smit, Erica ^{[1
,2
]}

Tameris, Michele ^{[1
,2
]}

Moyo, Sizulu ^{[1
,2
]}

Lang, Trudie ^{[3
]}

Veldsman, Ashley ^{[1
,2
]}

Hatherill, Mark ^{[1
,2
]}

van der Merwe, Linda ^{[1
,2
]}

Fletcher, Helen A. ^{[3
]}

Mahomed, Hassan ^{[1
,2
]}

Hill, Adrian V. S. ^{[3
]}

Hanekom, Willem A. ^{[1
,2
]}

Hussey, Gregory D. ^{[1
,2
]}

McShane, Helen ^{[3
]}

机构：

[1] Univ Cape Town, Inst Infect Dis & Mol Med, South African TB Vaccine Initiat, ZA-7700 Rondebosch, South Africa

[2] Univ Cape Town, Sch Child & Adolescent Hlth, ZA-7700 Rondebosch, South Africa

[3] Univ Oxford, Nuffield Dept Med, Ctr Clin Vaccinol & Trop Med, Oxford, England

来源：

JOURNAL OF INFECTIOUS DISEASES | 2008年 / 198卷 / 04期

基金：

英国惠康基金;

关键词：

D O I：

10.1086/590185

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. The efficacy of bacille Calmette-Guerin (BCG) may be enhanced by heterologous vaccination strategies that boost the BCG-primed immune response. One leading booster vaccine, MVA85A (where "MVA" denotes "modified vaccinia virus Ankara"), has shown promising safety and immunogenicity in human trials performed in the United Kingdom. We investigated the safety and immunogenicity of MVA85A in mycobacteria-exposed-but Mycobacterium tuberculosis-uninfected-healthy adults from a region of South Africa where TB is endemic. Methods. Twenty-four adults were vaccinated with MVA85A. All subjects were monitored for 1 year for adverse events and for immunological assessment. Results. MVA85A vaccination was well tolerated and induced potent T cell responses, as measured by interferon (IFN)-gamma enzyme-linked immunospot assay, which exceeded prevaccination responses up to 364 days after vaccination. BCG-specific CD4(+) T cells boosted by MVA85A were comprised of multiple populations expressing combinations of IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, and IL-17, as measured by polychromatic flow cytometry. IFN-gamma-expressing and polyfunctional IFN-gamma(+) TNF-alpha(+) IL-2(+) CD4(+) T cells were boosted during the peak BCG-specific response, which occurred 7 days after vaccination. Conclusion. The excellent safety profile and quantitative and qualitative immunogenicity data strongly support further trials assessing the efficacy of MVA85A as a boosting vaccine in countries where TB is endemic. Trial registration. ClinicalTrials. gov identifier: NCT00460590.

引用

页码：544 / 552

页数：9

共 46 条

[1] Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].