Madhi Shabir A, Koen Anthonet, Jose Lisa, van Niekerk Nadia, Adrian Peter V, Cutland Clare, François Nancy, Ruiz-Guiñazú Javier, Yarzabal Juan-Pablo, Moreira Marta, Borys Dorota, Schuerman Lode
aMedical Research Council: Respiratory and Meningeal Pathogens Research Unit bDepartment of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa cNational Institute for Communicable Diseases: a Division of the National Health Laboratory Service, Johannesburg, South Africa dGSK, Wavre, Belgium.
Medicine (Baltimore). 2017 Jan;96(2):e5881. doi: 10.1097/MD.0000000000005881.
Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children.
Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9-10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster.
Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related.
PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status.
在南非开展的一项III期、开放标签、单中心对照研究（ClinicalTrials.gov：NCT00829010），以评估10价肺炎球菌非分型流感嗜血杆菌蛋白D结合疫苗（PHiD-CV）在感染人类免疫缺陷病毒（HIV）的儿童（HIV+）、暴露于HIV但未感染的儿童（HEU）和未暴露于HIV且未感染的儿童（HUU）中的免疫原性、反应原性和安全性。
根据HIV状态分层的儿童接受PHiD-CV基础疫苗接种（6/10/14周龄；与常规儿童疫苗同时接种）和加强剂量（9-10月龄）。使用酶联免疫吸附试验和功能测定评估免疫反应，并在加强免疫后14个月内评估安全性。
HIV+组、HEU组和HUU组分别有83名、101名和100名儿童入组，70名、91名和93名儿童纳入符合方案免疫原性队列。对于每种疫苗血清型，基础疫苗接种后1个月抗体浓度≥0.2μg/mL的儿童百分比≥97%，加强免疫后1个月≥98.5%（两个时间点的6B和23F血清型除外）。基础疫苗接种后，HIV+儿童的功能性抗体反应较低：对于每种疫苗血清型，吞噬活性（OPA）滴度≥8的HIV+、HEU和HUU儿童百分比分别≥72%、≥81%和≥79%。加强免疫后，每组≥87%的儿童OPA滴度≥8。各组间反应原性相似。31名（37%）HIV+、25名（25%）HEU和20名（20%）HUU儿童报告了≥1次严重不良事件。5名HIV+儿童和4名HEU儿童死亡。1例死亡（婴儿猝死综合征；HEU组；第1剂后3天）被认为可能与疫苗有关。
PHiD-CV在HIV+、HEU和HUU儿童中具有免疫原性且耐受性良好，无论HIV感染状态如何都有可能带来显著益处。
