MICA:The immunogenicity of combined pertussis-containing vaccine (Tdap) for HIV-infected pregnant women and their newborns-A Randomized Clinical Trial

这项研究将研究是否在乌干达孕妇接种百日咳疫苗可能有助于防止乌干达婴儿生病或死于百日咳。乌干达等国的婴儿通常在10、14和16周时接种百日咳疫苗，在这些注射完成之前，婴儿有感染百日咳、身体不适或死亡的风险。在婴儿完全接种疫苗之前，他们依赖于自己的未成熟血细胞，以及在怀孕期间以母亲抗体的形式通过胎盘传递的保护。我们可以保护这些脆弱的婴儿的一种方法是给孕妇接种一种叫做Tdap的百日咳疫苗，以增加母亲血液中的抗体水平，这样更多的保护就可以通过胎盘进入婴儿。这已经在美国和英国这样的国家进行了，我们知道这对减少患百日咳的婴儿数量是有效的。世卫组织建议向世界各地的孕妇提供Tdap。然而，目前还没有研究表明，在乌干达等艾滋病负担很高的国家接种疫苗是否会以同样的方式起作用。我们知道，给孕妇接种百日咳疫苗可能会降低婴儿对自身疫苗的反应，这可能会使婴儿得不到保护。然而，乌干达的婴儿接受了与英国/美国婴儿不同类型的百日咳疫苗（wP）。这种疫苗被认为在百日咳高发的国家更有效。我们不知道在接种wP疫苗的国家是否也会出现同样的保护作用降低。许多因素会影响怀孕期间母亲对婴儿的保护程度。一个非常重要的因素是母亲是否感染了艾滋病毒。乌干达大约10%的孕妇感染了艾滋病毒，因此我们需要了解感染艾滋病毒的母亲是否与未感染艾滋病毒的母亲对百日咳疫苗有相同的反应，以及他们是否将相同数量的保护传递给婴儿。我们将通过邀请一组HIV感染和未感染HIV的孕妇参与我们的疫苗试验来研究这些重要问题。我们将为每个群体的一半人接种破伤风和百日咳疫苗，并为每个群体的一半人接种常规破伤风疫苗，乌干达的孕妇已经接种了这种疫苗。然后，我们将测量分娩时母亲血液中的抗体水平以及婴儿脐带血中的抗体水平。然后，我们可以测量有多少抗体从母亲传给婴儿。我们将比较HIV阴性和HIV阳性妇女之间的抗体水平。然后，我们将对所有婴儿进行随访，并在常规疫苗接种疗程结束时测量他们的百日咳抗体反应，以了解母亲接种疫苗是否影响了婴儿的保护水平。在乌干达为期24个月的研究中，我们将回答以下问题，以帮助决定是否应该使用母亲接种疫苗来保护乌干达等国家最脆弱的婴儿：1）与未感染艾滋病毒的妇女相比，感染艾滋病毒的孕妇对破伤风、白喉、无细胞百日咳（Tdap）疫苗的免疫应答是否较低？2)妊娠期接种Tdap疫苗是否会影响婴儿接种全细胞百日咳（wP）疫苗后产生的抗体量？

This study will work out whether vaccinating pregnant women in Uganda with a pertussis (whooping cough) vaccine might be useful to help prevent babies in Uganda from becoming ill or dying with whooping cough. Babies in countries like Uganda are usually vaccinated against pertussis at 10, 14 and 16 weeks of age, and until these injections are completed, babies are at risk of getting pertussis infection and becoming unwell or dying. Until a baby is fully vaccinated, they rely on their own immature blood cells and also protection passed across the placenta in the form of antibodies from their mother during pregnancy. One way that we could protect these vulnerable babies is by vaccinating pregnant women with a whooping cough vaccine called Tdap, to increase the antibody levels in the mother's blood so that more protection can pass across the placenta into the baby. This is already being done in countries like the U.S and the U.K, and we know it is effective in reducing the number of babies becoming sick with whooping cough. The WHO has recommended that Tdap be offered to pregnant women around the world. However, there are no studies looking at whether giving the vaccine in countries like Uganda, where there is a high burden of HIV disease, will work in the same way. We know that vaccinating a pregnant woman with pertussis vaccine may reduce a baby's response to their own vaccines, which could leave the baby unprotected. However, babies in Uganda receive a different type of pertussis vaccine (wP) to the one used for babies in the U.K/U.S. This vaccine is thought to be more effective in countries where there is a lot of pertussis. We do not know if the same reduced protective effect occurs in countries giving wP vaccine. Many factors affect how much protection is passed from a mother to her baby during pregnancy. A very important factor is whether or not the mum has HIV infection. Around 10% of pregnant women in Uganda have HIV and so we need to see if a mother with HIV has the same response to the whooping cough vaccine as a mother without HIV, and whether they pass the same amount of protection to their babies. We will study these important questions by asking a group of HIV-infected and HIV-uninfected pregnant women to be part of our vaccine trial. We will vaccinate half of each group with tetanus and whooping cough vaccines, and half of each with the routine tetanus vaccine, which pregnant women in Uganda already receive. We will then measure the antibody levels in the mothers' blood at the time of delivery and the antibody levels in the baby's umbilical cord blood. We can then measure how much antibody is passed from mothers to their babies. We will compare the antibody levels between HIV-negative and HIV-positive women. We will then follow-up all the babies, and measure their whooping cough antibody responses at the end of their routine vaccination course, to find out whether vaccinating their mothers has influenced the infant's protection levels.Throughout this 24 month study in Uganda we will answer the following questions to help decide whether maternal vaccination should be used to protect the most vulnerable babies in countries like Uganda:1) Do pregnant women with HIV have lower antibody responses to immunization with tetanus, diphtheria, acellular pertussis (Tdap) vaccine, compared to HIV-uninfected women?2) Does immunization with Tdap vaccine in pregnancy influence the amount of antibody an infant makes following the whole cell pertussis (wP) vaccine in babies.