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

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa.
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DOI:
10.1086/590185
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发表时间:
2008-08-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
McShane H
McShane H
中科院分区:
其他
文献类型:
--
作者:
Hawkridge T;Scriba TJ;Gelderbloem S;Smit E;Tameris M;Moyo S;Lang T;Veldsman A;Hatherill M;Merwe Lv;Fletcher HA;Mahomed H;Hill AV;Hanekom WA;Hussey GD;McShane H

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通过异种疫苗接种策略增强卡介苗的免疫反应,可以提高卡介苗的效力。一种领先的强化疫苗MVA85A在英国人体试验中显示出良好的安全性和免疫原性。我们研究了MVA85A在南非结核病流行地区暴露于分枝杆菌但未感染结核分枝杆菌的健康成年人中的安全性和免疫原性。24名成人接种了MVA85A疫苗。对所有受试者进行为期一年的不良反应和免疫学评估。MVA85A疫苗耐受性良好,通过干扰素-γELISPOT试验检测,在接种后364d,T细胞应答超过了接种前的水平。多色流式细胞术检测,MVA85A刺激的卡介苗特异性T细胞由多种表达干扰素-γ、肿瘤坏死因子-α、白介素2和白介素17的组合组成。免疫后7d,卡介苗特异性应答高峰期,干扰素-γ表达增强,多功能干扰素-γ+肿瘤坏死因子-α+IL-2+CD4+T细胞功能增强。良好的安全性以及定量和定性的免疫原性数据有力地支持了进一步的试验,以评估MVA85A作为加强疫苗在结核病流行国家的有效性。
The efficacy of BCG may be enhanced by heterologous vaccination strategies that boost the BCG-primed immune response. One leading booster vaccine, MVA85A, has shown promising safety and immunogenicity in UK human trials. We investigated the safety and immunogenicity of MVA85A in mycobacteria-exposed, but Mycobacterium tuberculosis-uninfected, healthy adults from a TB-endemic region of South Africa. Twenty-four adults were vaccinated with MVA85A. All subjects were followed up for one year for adverse events and for immunological assessment. MVA85A vaccination was well tolerated and induced potent T cell responses, measured by IFN-γ ELISPOT assay, which exceeded pre-vaccination levels up to 364 days after vaccination. BCG-specific CD4+ T cells boosted by MVA85A comprised of multiple populations expressing combinations of IFN-γ, TNF-α, IL-2 and IL-17, as measured by polychromatic flow cytometry. IFN-γ expressing and polyfunctional IFN-γ+TNF-α+IL-2+ CD4+ T cells were boosted during the peak BCG-specific response 7 days post-vaccination. The excellent safety profile and quantitative and qualitative immunogenicity data strongly support further trials to assess the efficacy of MVA85A as a boosting vaccine in TB endemic countries.
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