Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.
Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.
复制标题
DOI：
10.1016/j.vaccine.2012.06.084
复制
发表时间：
2012-08-17
期刊：
影响因子：
5.5
通讯作者：
McShane, Helen
中科院分区：
文献类型：
--
作者：
Pathan, Ansar A.;Minassian, Angela M.;Sander, Clare R.;Rowland, Rosalind;Porter, David W.;Poulton, Ian D.;Hill, Adrian V. S.;Fletcher, Helen A.;McShane, Helen
我们比较了3剂候选TB疫苗MVA 85 A。所有剂量的疫苗都是安全的，并诱导了Th 1型免疫应答。最强和最持久的反应是在最高剂量的MVA 85 A下观察到的。MVA 85 A高剂量1 × 108 PFU是安全的，可诱导持续免疫。一项非随机、开放标签、I期安全性和免疫原性剂量探索研究，旨在评估候选结核疫苗（表达结核分枝杆菌（MTB）抗原85 A的改良安卡拉牛痘病毒（MVA 85 A））在既往接种过BCG的健康成人志愿者中的安全性和免疫原性。健康的卡介苗接种志愿者接种1 × 107或1 × 108 PFU的MVA 85 A。记录所有不良事件，并使用离体IFN-γ ELISPOT测定法测量抗原特异性T细胞应答。比较了2个剂量组之间的安全性和免疫原性，并与既往试验（其中给予了5 × 107 PFU MVA 85 A）进行了比较。在给予1 × 107或1 × 108 PFU的MVA 85 A后，未记录到严重不良事件。与5 × 107或1 × 107 PFU的MVA 85 A相比，1 × 108 PFU的MVA 85 A给药后更常报告全身不良事件，但严重程度为轻度或中度，并在免疫后7天内完全消退。与5 × 107和1 × 107剂量相比，接受1 × 108 PFU的成人在免疫后通过IFN-γ ELISPOT测量的抗原特异性T细胞应答显著更高。此外，在1 × 108 PFU的MVA 85 A后，检测到更广泛的Ag 85 A表位。较高剂量的1 × 108 PFU MVA 85 A耐受性良好，增加了免疫后检测到的分泌IFN-γ的T细胞的频率，并扩大了检测到的Ag 85 A表位的范围。
► We compared 3 doses of a the candidate TB vaccine MVA85A. ► All doses of the vaccine were safe and induced a Th1 type immune response. ► The strongest and most sustained response was seen with the highest dose of MVA85A. ► A high dose of 1 × 108 PFU of MVA85A is safe and induces sustained immunity. A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. Healthy BCG-vaccinated volunteers were vaccinated with either 1 × 107 or 1 × 108 PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5 × 107 PFU MVA85A had been administered. There were no serious adverse events recorded following administration of either 1 × 107 or 1 × 108 PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1 × 108 PFU of MVA85A when compared to either 5 × 107 or 1 × 107 PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1 × 108 PFU compared to the 5 × 107 and 1 × 107 doses. Additionally, a broader range of Ag85A epitopes are detected following 1 × 108 PFU of MVA85A. A higher dose of 1 × 108 PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected.
登录
查看更多内容
影响因子：
3.7
作者：
Griffiths KL;Pathan AA;Minassian AM;Sander CR;Beveridge NE;Hill AV;Fletcher HA;McShane H
通讯作者：
McShane H
影响因子：
5.4
作者：
Beveridge, Natalie E. R.;Price, David A.;McShane, Helen
通讯作者：
McShane, Helen
影响因子：
6.4
作者：
Scriba, Thomas J.;Tameris, Michele;McShane, Helen
通讯作者：
McShane, Helen
影响因子：
--
作者：
de Cassan, Simone C.;Pathan, Ansar A.;Fletcher, Helen A.
通讯作者：
Fletcher, Helen A.
DOI：
10.1086/590185
发表时间：
2008-08-15
期刊：
The Journal of infectious diseases
影响因子：
--
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
通讯作者：
McShane H