Background

Pneumococcus remains an important cause of morbidity in pregnant women with HIV and their infants. We compared the safety and immunogenicity of PCV-10 and PPV-23 with placebo administered in pregnancy.

Methods

This double-blind, multicentre, randomised controlled trial was done at eight outpatient clinics in Brazil. Eligible participants were adult women with HIV who were pregnant at a gestational age between 14 weeks and less than 34 weeks and who were taking antiretroviral therapy at study entry. Participants were randomly assigned (1:1:1) to receive either PCV-10, PPV-23, or placebo. Participants and study teams were unaware of treatment allocation. Antibodies against seven vaccine serotypes in PCV-10 and PPV-23 were measured by ELISA. The primary outcomes were maternal and infant safety assessed by the frequency of adverse events of grade 3 or higher; maternal seroresponse (defined as ≥2-fold increase in antibodies from baseline to 28 days after immunisation) against five or more serotypes; and infant seroprotection (defined as anti-pneumococcus antibody concentration of ≥0·35 μg/mL) against five or more serotypes at 8 weeks of life. The study was powered to detect differences of 20% or higher in the primary immunological outcomes between treatment groups. This trial is registered with ClinicalTrials.gov, NCT02717494.

Findings

Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, of whom 116 were randomly assigned to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant in the PCV-10 group did not receive the vaccine and was excluded from subsequent analyses. The frequency of adverse events of grade 3 or higher during the first 4 weeks was similar in the vaccine and placebo groups (3% [90% CI 1–7] for the PCV-10 group, 2% [0–5] for the PPV-23 group, and 3% [1–8] for the placebo group). However, injection site and systemic grade 2 adverse reactions were reported more frequently during the first 4 weeks in the vaccine groups than in the placebo group (14% [9–20] for the PCV-10 group, 7% [4–12] for the PPV-23 group, and 3% [1–7] for the placebo group). The frequency of grade 3 or higher adverse effects was similar across maternal treatment groups (20% [14–27] for the PCV-10 group, 21% [14–28] for the PPV-23 group, and 20% [14–27] for the placebo group). Seroresponses against five or more serotypes were present in 74 (65%) of 114 women in the PCV-10 group, 72 (65%) of 110 women in the PPV-23 group, and none of the 113 women in the placebo group at 4 weeks post vaccination (p<0·0001 for PPV-23 group vs placebo and PCV-10 group vs placebo). Seroresponse differences of 20% or higher in vaccine compared with placebo recipients persisted up to 24 weeks post partum. At birth, 76 (67%) of 113 infants in the PCV-10 group, 62 (57%) of 109 infants in the PPV-23 group, and 19 (17%) of 115 infants in the placebo group had seroprotection against five or more serotypes (p<0·0001 for PPV-23 vs placebo and PCV-10 vs placebo). At 8 weeks, the outcome was met by 20 (19%) of 108 infants in the PCV-10 group, 24 (23%) of 104 infants in the PPV-23 group, and one (1%) of 109 infants in the placebo group (p<0·0001). Although a difference of 20% or higher compared with placebo was observed only in the infants who received PPV-23 at 8 weeks of life, the difference between the two vaccine groups was not appreciable.

Interpretation

PCV-10 and PPV-23 were equally safe and immunogenic in pregnant women with HIV and conferred similar levels of seroprotection to their infants. In areas in which childhood PCV administration decreased the circulation of PCV serotypes, PPV-23 administration to pregnant women with HIV might be more advantageous than PCV by virtue of including a broader range of serotypes.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.

中文翻译：

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感染 HIV 的孕妇接种结合疫苗和多糖肺炎球菌疫苗的安全性、免疫原性和经胎盘抗体转运：一项多中心随机对照试验

背景

肺炎球菌仍然是感染 HIV 的孕妇及其婴儿发病的一个重要原因。我们比较了 PCV-10 和 PPV-23 与妊娠期安慰剂的安全性和免疫原性。

方法

这项双盲、多中心、随机对照试验在巴西的八家门诊进行。符合条件的参与者是感染 HIV 的成年女性，她们怀孕的胎龄在 14 周到 34 周之间，并且在研究开始时正在接受抗逆转录病毒治疗。参与者被随机分配 (1:1:1) 接受 PCV-10、PPV-23 或安慰剂。参与者和研究团队不知道治疗分配。通过ELISA测量PCV-10和PPV-23中针对七种疫苗血清型的抗体。主要结局是通过 3 级或更高级别的不良事件频率评估的母婴安全性；针对五种或更多血清型的母体血清反应（定义为从基线到免疫后 28 天抗体增加≥2 倍）；和婴儿血清保护（定义为 ≥0·35 μg/mL 的抗肺炎球菌抗体浓度）在出生 8 周时针对五种或更多血清型。该研究旨在检测治疗组之间主要免疫结果的 20% 或更高的差异。该试验已在 ClinicalTrials.gov 注册，NCT02717494。

发现

在 2016 年 4 月 1 日至 2017 年 11 月 30 日期间，我们招募了 347 名感染 HIV 的孕妇，其中 116 名被随机分配到 PCV-10 组，115 名被分配到 PPV-23 组，116 名被分配到安慰剂组。PCV-10 组的一名参与者没有接种疫苗，因此被排除在后续分析之外。疫苗组和安慰剂组在前 4 周内 3 级或更高级别的不良事件发生率相似（PCV-10 组为 3% [90% CI 1-7]，PCV-10 组为 2% [0-5] PPV-23 组，安慰剂组为 3% [1-8]）。然而，在疫苗组的前 4 周内，注射部位和全身 2 级不良反应的报告频率高于安慰剂组（PCV-10 组为 14% [9-20]，7% [4-12] PPV-23 组和安慰剂组 3% [1-7]）。3 级或更高级别不良反应的频率在孕产妇治疗组中相似（PCV-10 组为 20% [14-27]，PPV-23 组为 21% [14-28]，以及 20% [14- 27]安慰剂组）。PCV-10 组 114 名女性中的 74 名（65%）、PPV-23 组 110 名女性中的 72 名（65%）和安慰剂组 113 名女性中均未出现针对五种或更多血清型的血清反应。接种后 4 周（PPV-23 组 p<0·0001vs安慰剂和 PCV-10 组vs安慰剂）。与安慰剂接受者相比，疫苗接种后 20% 或更高的血清反应差异持续到产后 24 周。出生时，PCV-10 组 113 名婴儿中的 76 名（67%）、PPV-23 组 109 名婴儿中的 62 名（57%）和安慰剂组 115 名婴儿中的 19 名（17%）对 5或更多血清型（PPV-23对比安慰剂和 PCV-10对比p<0·0001安慰剂）。在 8 周时，PCV-10 组 108 名婴儿中的 20 名（19%）、PPV-23 组 104 名婴儿中的 24 名（23%）和 109 名婴儿中的 1 名（1%）达到了结果。安慰剂组 (p<0·0001)。尽管仅在出生 8 周时接受 PPV-23 的婴儿中观察到与安慰剂相比有 20% 或更高的差异，但两个疫苗组之间的差异并不明显。

解释

PCV-10 和 PPV-23 在感染 HIV 的孕妇中同样安全且具有免疫原性，并赋予其婴儿相似水平的血清保护作用。在儿童期 PCV 给药减少 PCV 血清型循环的地区，由于包含更广泛的血清型，PPV-23 对 HIV 感染孕妇的给药可能比 PCV 更有利。

资金

Eunice Kennedy Shriver国家儿童健康与人类发展研究所。

翻译

有关摘要的葡萄牙语翻译，请参阅补充材料部分。