本帖最後由 goodcat1111 於 2009-4-30 15:04 編輯
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
April 7, 2009 — 根據一項發表在4月15日美國呼吸與重症醫學期刊的研究結果，一種新的結核病（TB）疫苗（MVA85A）對於潛伏TB感染（LTBI）病患來說是安全的，且具高度免疫性。
英國牛津大學Clare R. Sander與其同事寫到，一個有效的新TB疫苗療程必須對於罹患LTBI病患來說是安全的，且具公共衛生照護的優先性。目前亟需一個新的TB疫苗，MVA85A是第一個在結核分枝桿菌潛伏感染受試者身上評估的新疫苗。
這項開放標記、第一期臨床研究的參與者是來自倫敦或是牛津TB聯繫診所、或是在牛津醫院所張貼的廣告海報招募而來的12位罹患LTBI病患，使用基因重組修飾疫苗Ankara表現抗原85A（MVA85A）。在為期52週的試驗期間，這些病患接受MVA85A疫苗接種，並且接受臨床與提供血液樣本進行免疫分析以及螢光活化細胞收集研究。在試驗前與接種疫苗10週後，進行胸腔電腦斷層（CT）。以臨床、放射學、發炎標記來決定MVA85A的安全性。
在罹患LTBI的病患身上，MVA85A是安全的，不良反應發生率與過去使用MVA85A的研究相似，且在接種疫苗後，發炎指標或是胸腔CT沒有發現顯著變化。對MVA85A的強烈抗原專一INF-gamma反應與IL-2反應持續達52週，IFN-gamma反應幅度與過去使用MVA85A於Calmette-Gu?rin桿菌（BCG）接種個體的過去研究相似。
在接種疫苗前，可以偵測到抗原85A專一多工CD41 T細胞，且在接種疫苗後，這些細胞數目顯著增加。
研究作者寫到，MVA85A對罹患LTBI病患來說是安全的、且具高度免疫作用。這些結果將會加速在TB流行區域未來的研究。
這項研究的限制包括使用的群眾差異性大，且樣本數目較小。
在隨後的主編評論中，英國倫敦衛生與熱帶醫學學院Hazel M. Dockrell博士與馬里蘭約翰霍普金斯彭博公衛學院的Ying Zhang醫師表示，需要未來的研究來評估MVA85A的療效。
Dockrell博士與Zhang醫師寫到，除了安全性與療效外，研究者們需要證實刺激免疫反應的效果還有比BCG更好的保護效果，特別是在BCG被證實無法預防肺部結核病的狀況下。為了讓我們距離更有效疫苗的目標更近，這些新的疫苗應該在罹患LTBI病患身上進行測試，而最近的MVA85A研究結果將可以協助這個新疫苗前進到疫苗研發線上。
這項研究由牛津生物醫學研究中心贊助。兩位研究作者是Wellcome研究者，而第三位作者由AFTBVAC（EU第五架構）贊助。研究作者其中三位是牛津大學該成分專利發明者。Dockrell醫師與Zhang醫師表示沒有相關資金上的往來。
New TB Vaccine Is Safe, Highly Immunogenic in Patients With Latent Infection
By Laurie Barclay, MD
Medscape Medical News
April 7, 2009 — A new tuberculosis (TB) vaccine (MVA85A) is safe and highly immunogenic in individuals with latent TB infection (LTBI), according to the results of a study reported in the April 15 issue of the American Journal of Respiratory and Critical Care Medicine.
"An effective new [TB] vaccine regimen must be safe in individuals with [LTBI] and is a priority for global health care," write Clare R. Sander, from the University of Oxford, United Kingdom, and colleagues. "There has never been a more urgent need for a new [TB] vaccine. MVA85A is the first new vaccine to be evaluated in Mycobacterium tuberculosis latently infected subjects."
This open-label, phase 1 trial studied recombinant modified vaccinia Ankara expressing antigen 85A (MVA85A) in 12 patients with LTBI who were recruited from TB contact clinics in Oxford and London or from poster advertisements in Oxford hospitals. During a 52-week period after vaccination with MVA85A, patients were evaluated clinically and provided blood samples for immunological analysis using interferon gamma (IFN-gamma) and interleukin 2 (IL-2) enzyme-linked immunosorbent spot assays and fluorescence-activated cell sorting. At baseline and at 10 weeks after vaccination, thoracic computed tomography (CT) was performed. Clinical, radiological, and inflammatory markers allowed determination of MVA85A safety.
In these patients with LTBI, MVA85A was safe, with adverse events similar to those reported in previous trials of MVA85A, and no clinically significant changes after vaccination in inflammatory markers or thoracic CT. There was a strong antigen-specific IFN-gamma and IL-2 response to MVA85A that persisted for 52 weeks, with the magnitude of IFN-gamma response similar to that seen in previous trials of MVA85A in bacillus Calmette-Guin (BCG)-vaccinated individuals.
Before vaccination, antigen 85A–specific polyfunctional CD41 T cells could be detected, and there were statistically significant increases in numbers of these cells after vaccination.
"MVA85A is safe and highly immunogenic in individuals with LTBI," the study authors write. "These results will facilitate further trials in TB-endemic areas."
Limitations of this study include the heterogeneity of the population used and the small sample size.
In an accompanying editorial, Hazel M. Dockrell, PhD, from the London School of Hygiene and Tropical Medicine, United Kingdom, and Ying Zhang, MD, PhD, from the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, note that future studies are needed to evaluate the efficacy of MVA85A.
"Beyond safety and efficacy, [the investigators] need to show not only immunogenicity, but improved protective efficacy over BCG and particularly in settings in which BCG has proved ineffective at protecting against pulmonary [TB]," Dr. Dockrell and Dr. Zhang write. "To move us closer to our goal of a more effective vaccine, these new vaccines have to be tested in individuals with [LTBIs], and the recent MVA85A results will help this new vaccine move down the vaccine development pipeline."
Funds from the Oxford Biomedical Research Centre supported this study. Two study authors are Wellcome fellows, and a third author was supported by AFTBVAC (EU 5th framework). Three of the study authors are named inventors on a composition of matter patent for MVA85A filed by the University of Oxford. Dr. Dockrell and Dr. Zhang have disclosed no relevant financial relationships.
Am J Respir Crit Care Med. 2009;179;724–733. |
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