Ross T M, Xu Y, Bright R A, Robinson H L
Yerkes Regional Primate Research Center, Division of Microbiology and Immunology, Emory University, Atlanta, GA 30329, USA.
Nat Immunol. 2000 Aug;1(2):127-31. doi: 10.1038/77802.
The ability of the C3d component of complement to enhance antibody responses and protective immunity to influenza virus challenges was evaluated using a DNA vaccine encoding a C3d fusion of the hemagglutinin (HA) from influenza virus. Plasmids were generated that encoded a transmembrane HA (tmHA), a secreted form of HA (sHA), or a sHA fused to three tandem copies of the murine homologue of the C3d (sHA-3C3d). Analysis of the titers, avidity maturation, and hemagglutinin-inhibition activity of raised antibody revealed that immunizations with sHA-3C3d DNA accelerated both the avidity maturation of antibody to HA and the appearance of hemagglutinin-inhibition activity. These accelerated antibody responses correlated to a more rapid appearance of protective immunity. They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA.
利用编码来自流感病毒血凝素(HA)的C3d融合体的DNA疫苗,评估补体C3d成分增强抗体反应以及对流感病毒攻击的保护性免疫的能力。构建了编码跨膜HA(tmHA)、分泌形式的HA(sHA)或与C3d小鼠同源物的三个串联拷贝融合的sHA(sHA-3C3d)的质粒。对产生的抗体的滴度、亲和力成熟度和血凝素抑制活性的分析表明,用sHA-3C3d DNA进行免疫接种加速了抗体对HA的亲和力成熟以及血凝素抑制活性的出现。这些加速的抗体反应与保护性免疫的更快出现相关。它们还与以比非C3d形式的HA的保护剂量低十倍的剂量进行单次接种就能完全抵抗活病毒攻击相关。