Forns X, Emerson S U, Tobin G J, Mushahwar I K, Purcell R H, Bukh J
Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0740, USA.
Vaccine. 1999 Apr 9;17(15-16):1992-2002. doi: 10.1016/s0264-410x(98)00448-4.
We analyzed the humoral immune response elicited by hepatitis C virus (HCV) E2 protein expressed in vivo after injection of plasmid DNA into mice and rhesus macaques. Three plasmids were used for immunization: a plasmid containing the entire sequence of the E2 and p7 genes (pE2); a plasmid encoding a truncated form of the E2 protein targeted to the cell surface (pE2surf); a control plasmid (pDisplay) lacking an HCV insert. Each plasmid was injected intramuscularly into 5 mice and intraepidermally (via gene gun) into 5 mice. Immunization was repeated three times at three week intervals. Five macaques were injected intramuscularly (two with pE2, two with pE2surf and one with pDisplay) and immunization was repeated after 8 weeks. All mice immunized via gene gun with pE2 or pE2surf developed anti-E2. The animals immunized with pE2surf developed an earlier and stronger humoral immune response than those immunized with pE2. Only 2 of the mice injected by the intramuscular route, both immunized with pE2surf, developed detectable anti-E2. One of the two macaques immunized with pE2 and both macaques immunized with pE2surf developed anti-E2; the humoral immune response was much stronger in the animals immunized with pE2surf. Our results suggest that presentation of HCV E2 on the cell surface may increase its immunogenicity while preserving its ability to react with antibodies generated during a natural infection.
我们分析了将质粒DNA注射到小鼠和恒河猴体内后，体内表达的丙型肝炎病毒（HCV）E2蛋白引发的体液免疫反应。使用了三种质粒进行免疫：一种包含E2和p7基因完整序列的质粒（pE2）；一种编码靶向细胞表面的截短形式E2蛋白的质粒（pE2surf）；一种缺乏HCV插入片段的对照质粒（pDisplay）。每种质粒分别肌肉注射到5只小鼠体内，并通过基因枪表皮内注射到5只小鼠体内。每隔三周重复免疫三次。对5只恒河猴进行肌肉注射（2只注射pE2，2只注射pE2surf，1只注射pDisplay），8周后重复免疫。所有通过基因枪用pE2或pE2surf免疫的小鼠都产生了抗E2抗体。用pE2surf免疫的动物比用pE2免疫的动物产生了更早、更强的体液免疫反应。肌肉注射途径的小鼠中，只有2只（均用pE2surf免疫）产生了可检测到的抗E2抗体。用pE2免疫的2只恒河猴中的1只以及用pE2surf免疫的2只恒河猴都产生了抗E2抗体；用pE2surf免疫的动物体液免疫反应更强。我们的结果表明，HCV E2在细胞表面的呈递可能会增加其免疫原性，同时保留其与自然感染期间产生的抗体发生反应的能力。
