The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.
The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.
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DOI：
10.1371/journal.pone.0136500
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Orme IM
中科院分区：
文献类型：
--
作者：
Henao-Tamayo M;Shanley CA;Verma D;Zilavy A;Stapleton MC;Furney SK;Podell B;Orme IM
迄今为止，大多数针对结核分枝杆菌的新疫苗，包括当前卡介苗的新重组版本，通常都是针对实验室菌株H37Rv或Erdman进行筛选的。在这项研究中，我们利用我们最近的工作来表征越来越多的新出现的临床分离株[来自美国或南非西开普省地区]，以确定疫苗对这些[主要是高毒力]菌株的保护程度。我们在这里展示了BCG巴斯德和重组BCG AERS-422[这里用作新一代BCG疫苗的一个很好的例子]在小鼠和豚鼠低剂量气溶胶感染模型中对大多数临床分离株具有良好的保护作用。然而，与BCG巴斯德相比，AERAS-422在长期存活试验中并不有效。对所有测试的西开普省菌株都表现出非常强烈的保护作用，这强化了我们的观点，即任何提高卡介苗的尝试都很难在统计上实现。这一观察是在其他人越来越多的论点的背景下讨论的，即最近的一项疫苗试验的失败取消了进一步使用动物模型来预测疫苗效力的资格。在我们看来，这种观点是完全错误的，试验地点地区流行菌株的适合性是核心重要因素，而该领域并未解决这一问题。
To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.