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两项随机对照试验中,成人对甲型H1N1流感大流行病毒疫苗的细胞介导和体液反应的长期持续性以及AS03佐剂系统的作用

Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09 Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults during Two Randomized Controlled Trials.

作者信息

van der Most Robbert G, Clément Frédéric, Willekens Julie, Dewé Walthère, Walravens Karl, Vaughn David W, Leroux-Roels Geert

机构信息

GSK Vaccines, Rixensart, Belgium

Center for Vaccinology, Ghent University and University Hospital, Ghent, Belgium.

出版信息

Clin Vaccine Immunol. 2017 Jun 5;24(6). doi: 10.1128/CVI.00553-16. Print 2017 Jun.

Abstract

We investigated the role of AS03 (here AS03), an α-tocopherol oil-in-water emulsion-based adjuvant system, on the long-term persistence of humoral and cell-mediated immune responses to A(H1N1)pdm09 influenza vaccines. In two studies, a total of 261 healthy adults (≤60 years old) were randomized to receive two doses of AS03-adjuvanted vaccine containing 3.75 μg of hemagglutinin (HA) or nonadjuvanted vaccine containing 15 μg of hemagglutinin (in study A) or 3.75 μg of hemagglutinin (in study B) 21 days apart. Hemagglutination inhibition (HI) antibody, memory B-cell, and CD4/CD8 T-cell responses were characterized up to 1 year following dose 1. We also assessed the effects of age and seasonal influenza vaccination history. AS03-adjuvanted (3.75 μg HA) vaccine and nonadjuvanted vaccine at 15 μg but not at 3.75 μg HA elicited HI antibody responses persisting at levels that continued to meet European licensure criteria through month 12. At month 12, the geometric mean titer for AS03-adjuvanted vaccine was similar to that for nonadjuvanted (15-μg) vaccine in study A (1:86 and 1:88, respectively) and higher than that for nonadjuvanted (3.75-μg) vaccine in study B (1:77 and 1:35, respectively). A(H1N1)pdm09-specific CD4 T-cell and B-cell responses were stronger in AS03-adjuvanted groups and persisted only in these groups for 12 months at levels exceeding prevaccination frequencies. Advancing age and a seasonal vaccination history tended to reduce HI antibody and memory B-cell responses and, albeit less consistently, CD4 T-cell responses. Thus, AS03 seemed to enhance the persistence of humoral and cell-mediated responses to A(H1N1)pdm09 vaccine, allowing for antigen sparing and mitigating potential negative effects of age and previous seasonal vaccination. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00968539 and NCT00989287.).

摘要

我们研究了AS03(此处指AS03),一种基于α-生育酚水包油乳液的佐剂系统,对A(H1N1)pdm09流感疫苗体液免疫和细胞介导免疫反应长期持续性的作用。在两项研究中,共有261名健康成年人(≤60岁)被随机分组,分别接受两剂含3.75μg血凝素(HA)的AS03佐剂疫苗或含15μg血凝素的无佐剂疫苗(研究A)或含3.75μg血凝素的无佐剂疫苗(研究B),间隔21天接种。在接种第1剂疫苗后的1年内,对血凝抑制(HI)抗体、记忆B细胞和CD4/CD8 T细胞反应进行了特征分析。我们还评估了年龄和季节性流感疫苗接种史的影响。含3.75μg HA的AS03佐剂疫苗和含15μg而非3.75μg HA的无佐剂疫苗引发的HI抗体反应在第12个月时仍持续保持在符合欧洲许可标准的水平。在第12个月时,研究A中AS03佐剂疫苗的几何平均滴度与无佐剂(15μg)疫苗相似(分别为1:86和1:88),且高于研究B中无佐剂(3.75μg)疫苗的几何平均滴度(分别为1:77和1:35)。A(H1N1)pdm09特异性CD4 T细胞和B细胞反应在AS03佐剂组中更强,且仅在这些组中持续12个月,其水平超过接种前频率。年龄增长和季节性疫苗接种史往往会降低HI抗体和记忆B细胞反应,并且对CD4 T细胞反应的影响虽不太一致但也有降低趋势。因此,AS03似乎增强了对A(H1N1)pdm09疫苗体液免疫和细胞介导免疫反应的持续性,从而实现抗原节约并减轻年龄和既往季节性疫苗接种的潜在负面影响。(这些研究已在ClinicalTrials.gov上注册,注册号为NCT00968539和NCT00989287。)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c3d/5461372/7c1cd7e2dfd3/zcd9990954870001.jpg

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