Nachman Sharon, Kim Soyeon, King James, Abrams Elaine J, Margolis David, Petru Ann, Shearer William, Smith Elizabeth, Moye Jack, Blanchard Suzette, Hawkins Elizabeth, Bouquin Pamela, Vink Peter, Benson Mindy, Estep Scharla, Malinoski Frank
Department of Pediatrics, State University of New York Health Science Center at Stony Brook, Stony Brook, New York 11794, USA.
Pediatrics. 2003 Jul;112(1 Pt 1):66-73. doi: 10.1542/peds.112.1.66.
Heptavalent pneumococcal conjugate vaccine (PCV) has been shown to be safe and effective in healthy infants and children. However, little is known about its use in children who have human immunodeficiency virus (HIV) infection and are known to be at increased risk of developing pneumococcal infections. This study was conducted to evaluate the safety and immunogenicity of heptavalent PCV in infants with HIV infection.
The Pediatric AIDS Clinical Trials Group Study 292 Team randomized infants with HIV infection 2:1 to receive heptavalent PCV or placebo in a double-blinded manner. Infants were vaccinated with 3 doses at 2-month intervals, starting at ages 56 to 180 days. A booster dose was given at 15 months of age. Immunogenicity was evaluated after the third dose of vaccine, before and after the booster dose, and at 24 months of age.
Thirty infants with HIV infection received PCV, and 15 received placebo. No differences in baseline characteristics were found across arms. Five severe acute reactions were experienced by 4 subjects: 3 in the PCV arm and 1 in the placebo arm; all occurred among subjects with symptomatic disease at study entry. No differences were found in the 2 arms with respect to the number or timing of new diagnoses through 24 months of age, including diagnoses of otitis media. However, when symptomatic subjects were examined separately, the first new diagnosis occurred more rapidly among PCV recipients. Three deaths, all judged to be unrelated to study vaccine, occurred during follow-up: 2 in the PCV arm and 1 in the placebo arm. The primary immunogenicity measures were based on composites of 4-fold changes in serotype-specific immunoglobulin G titers from preimmunization levels. We found a highly significant difference between the vaccine and placebo arms, with the PCV arm showing higher rates of response. Asymptomatic and symptomatic subjects who received PCV had similar immunologic responses for all serotypes.
This study demonstrates that heptavalent PCV was well tolerated and not associated with vaccine-associated adverse reactions. Most important, this vaccine was immunogenic in the infant with HIV infection. However, additional studies of this vaccine (or others) must pay special attention to patients with symptomatic HIV disease, as they seem to be at higher risk for adverse events to any antigen.
七价肺炎球菌结合疫苗（PCV）已被证明在健康婴幼儿中安全有效。然而，对于其在感染人类免疫缺陷病毒（HIV）且已知患肺炎球菌感染风险增加的儿童中的应用知之甚少。本研究旨在评估七价PCV在HIV感染婴儿中的安全性和免疫原性。
儿科艾滋病临床试验组研究292团队将HIV感染婴儿按2:1随机分组，以双盲方式接受七价PCV或安慰剂。婴儿从56至180日龄开始，每隔2个月接种3剂疫苗。在15月龄时给予加强剂量。在第三剂疫苗接种后、加强剂量接种前后以及24月龄时评估免疫原性。
30例HIV感染婴儿接受了PCV，15例接受了安慰剂。两组间基线特征无差异。4名受试者经历了5次严重急性反应：PCV组3例，安慰剂组1例；所有反应均发生在研究入组时患有症状性疾病的受试者中。两组在至24月龄的新诊断数量或时间方面，包括中耳炎诊断，均未发现差异。然而，当分别检查有症状的受试者时，PCV接种者中首次新诊断出现得更快。随访期间发生了3例死亡，均判定与研究疫苗无关：PCV组2例，安慰剂组1例。主要免疫原性指标基于血清型特异性免疫球蛋白G滴度相对于免疫前水平4倍变化的综合结果。我们发现疫苗组和安慰剂组之间存在高度显著差异，PCV组显示出更高的反应率。接受PCV的无症状和有症状受试者对所有血清型的免疫反应相似。
本研究表明七价PCV耐受性良好，且与疫苗相关不良反应无关。最重要的是，这种疫苗在HIV感染婴儿中具有免疫原性。然而，对这种疫苗（或其他疫苗）的进一步研究必须特别关注有症状的HIV疾病患者，因为他们似乎对任何抗原发生不良事件的风险更高。
