MVA85A Tuberculosis Vaccine Prime and Selective Delayed BCG Boost in Infants of HIV Infected Mothers

卡介苗对儿童肺结核病的保护作用有限。卡介苗接种对大多数新生儿来说是安全的，但即使接受抗逆转录病毒治疗(ART)，也可能导致感染艾滋病毒的婴儿出现严重的、往往是致命的并发症。世界卫生组织建议，不应该给已知感染艾滋病毒的婴儿服用卡介苗。然而，艾滋病毒检测直到6周大时才能准确，那时已经出生时已经接种了卡介苗。2009年，超过四分之一的南非婴儿是感染艾滋病毒的母亲所生。南非的年结核病发病率是世界上最高的，感染艾滋病毒母亲的孩子患结核病的风险特别高。正在开发和测试新的结核病疫苗(http://www.stoptb.org/wg/new_vaccines/).MVA85A是一种新的结核病疫苗，类似于天花疫苗，但添加了结核病蛋白。MVA85A疫苗已被证明是安全的，并在儿童和成人，包括艾滋病毒感染者中产生针对结核病的免疫反应。我们已经证明，如果卡介苗接种在出生后推迟几周，被认为对预防结核病至关重要的免疫反应将得到改善。如果在卡介苗后几周接种一种新的结核病疫苗，如MVA85A，免疫力也会得到提高。一些研究表明，无论是先接种卡介苗还是先接种新疫苗，对免疫力都没有影响。我们将在我们经验丰富的南非开普敦附近的结核病疫苗试验地点测试MVA85A疫苗是否可以在婴儿出生时接种，那里的艾滋病毒感染率和结核病发病率很高。这项试验将测试出生时接种MVA85A疫苗的安全性和免疫力，并与虚拟疫苗接种(安慰剂)进行比较，对340名感染艾滋病毒的母亲的婴儿进行为期一年的跟踪。只有那些被证实没有感染艾滋病毒的婴儿才会在8周大时接受延迟接种卡介苗。感染艾滋病毒的婴儿将受益于不接种卡介苗，这就是在感染艾滋病毒的母亲的婴儿中测试新生儿MVA85A疫苗的原因。如果我们证明，新生儿接种MVA85A疫苗几乎没有副作用，并对结核病产生良好的免疫反应，我们可能会继续测试这种新的结核病疫苗策略是否真的在所有婴儿中预防结核病，而不考虑母亲感染艾滋病毒。这些发现将对疫苗安全和预防儿童结核病至关重要，并可能导致全球婴儿疫苗接种计划的关键改进。

BCG vaccine offers limited protection against lung TB in children. BCG vaccination is safe for most newborn babies, but may cause severe, often fatal, complications in babies with HIV infection, even with antiretroviral treatment (ART). The WHO recommends that BCG should not be given to babies known to be HIV infected. However, HIV testing is not accurate until 6 weeks of age, when BCG has already been given at birth. More than one quarter of South African babies were born to HIV infected mothers in 2009. South Africa has the highest annual TB rate in the world and children of HIV infected mothers are at especially high risk of TB. New TB vaccines are being developed and tested (http://www.stoptb.org/wg/new_vaccines/). MVA85A is a new TB vaccine, similar to the smallpox vaccine, but with a TB protein added. MVA85A vaccine has been shown to be safe and generates an immune response against TB in children and adults, including people with HIV infection. We have shown that if BCG vaccination is delayed for several weeks after birth, the immune response thought to be important for protection against TB is improved. Immunity is also improved if a new TB vaccine, such as MVA85A, is given several weeks after BCG. Some studies suggest that it does not matter for immunity whether BCG or the new vaccine is given first. We will test whether MVA85A vaccine can be given to babies at birth, at our experienced TB vaccine trial sites near Cape Town, South Africa, where rates of HIV infection and TB are high. This trial will test the safety and immunity of MVA85A vaccination at birth, compared to a dummy vaccination (placebo), in 340 babies of HIV infected mothers, followed up for one year. Only those babies proven not to have HIV infection would receive delayed BCG vaccine at 8 weeks of age. HIV infected babies would benefit by not receiving BCG and this is the reason for testing newborn MVA85A vaccination among infants of HIV infected mothers. If we show that newborn MVA85A vaccination has few side-effects and generates a good immune response against TB, we may proceed to test whether this new TB vaccine strategy actually prevents TB, among all infants, regardless of maternal HIV infection. These findings will be critically important for vaccine safety, and prevention of childhood TB, and may lead to key improvements in the global infant vaccination schedule.