DNA 引物接种于流感灭活疫苗（H5N1）之前可增加抗体表位谱，并以增强间隔依赖性方式增加成年人中的亲和力成熟。
DNA priming prior to inactivated influenza A(H5N1) vaccination expands the antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults.
机构信息
Division of Viral Products,National Institute of Allergyand Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
出版信息
J Infect Dis. 2013 Aug 1;208(3):413-7. doi: 10.1093/infdis/jit178. Epub 2013 Apr 30.
Abstract
DNA priming improves the response to inactivated influenza A(H5N1) vaccination. We compared the immunogenicity of an H5 DNA prime (using strain A/Indonesia/5/2005) followed by an H5N1 monovalent inactivated vaccine boost at 4, 8, 12, 16, or 24 weeks to that of 2 doses of H5N1 monovalent inactivated vaccine in adults. Antibody epitope repertoires were elucidated by genome-fragment phage-display library analysis, and antibody avidities for HA1 and HA2 domains were measured by surface plasmon resonance. H5 DNA priming expanded the H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not the HA2) domain in an interval-dependent manner. Enhanced HA1 binding and avidity after an interval of ≥12 weeks between prime and boost correlated with improved neutralization of homologous and heterologous H5N1 strains. Clinical trials registration NCT01086657.
摘要
DNA 引物可提高灭活甲型流感病毒（H5N1）疫苗的应答效果。我们比较了 H5 DNA 引物（使用 A/印度尼西亚/5/2005 株）接种后，间隔 4、8、12、16 或 24 周接种 H5N1 单价灭活疫苗加强针与接种 2 剂 H5N1 单价灭活疫苗在成人中的免疫原性。通过基因组片段噬菌体展示文库分析阐明了抗体表位库，通过表面等离子体共振测量了针对 HA1 和 HA2 结构域的抗体亲和力。H5 DNA 引物以时间依赖性方式扩大了 H5 特异性抗体表位库，并增强了对 HA1（而非 HA2）结构域的抗体亲和力。在间隔≥12 周的时间内进行加强针之前，增强的 HA1 结合和亲和力与提高同源和异源 H5N1 株的中和作用相关。临床试验注册 NCT01086657。
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