Netski Dale M, Mosbruger Tim, Depla Erik, Maertens Geert, Ray Stuart C, Hamilton Robert G, Roundtree Stacy, Thomas David L, McKeating Jane, Cox Andrea
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Clin Infect Dis. 2005 Sep 1;41(5):667-75. doi: 10.1086/432478. Epub 2005 Jul 22.
There is little information on the timing, magnitude, specificity, and clinical relevance of the antibody response to acute hepatitis C virus (HCV) infection. We investigated the specificity, titer, and neutralizing potential of antibody responses to acute infection by examining 12 injection drug users before, during, and after infection.
Seroconversion was defined as incident detection of HCV-specific antibodies by using a commercially available enzyme-linked immuosorbent assay (ELISA). HCV protein-specific antibody responses were measured using recombinant antigens in an ELISA. For neutralization assays, plasma was incubated with human immunodeficiency virus (HIV)-HCV H77 or control HIV-murine leukemia virus (MLV) pseudotype virus and then allowed to infect Hep3B hepatoma cells.
The mean time to HCV seroconversion was 6 weeks after the onset of viremia. Antibody responses to nonstructural proteins were detected before responses to the structural proteins, and antibodies to both were primarily restricted to the immunoglobulin G1 (IgG1) subclass. The maximum median end point titers for antibody responses to structural and nonstructural proteins were 1 : 600 and 1 : 6400, respectively. Antibodies that neutralized a retroviral pseudotype bearing HCV 1a envelope glycoproteins were detected at seroconversion in only 1 subject and at 6-8 months after seroconversion in 3 subjects. The delayed appearance of neutralizing antibodies was consistent with the late development of antibodies specific for the viral envelope glycoproteins, which are believed to mediate virus neutralization.
The humoral immune response to acute HCV infection is of relatively low titer, is restricted primarily to the IgG1 subclass, and is delayed. A better understanding of why production of neutralizing antibody is delayed may improve efforts to prevent HCV infection.
关于急性丙型肝炎病毒（HCV）感染后抗体反应的时间、强度、特异性及临床相关性的信息较少。我们通过检测12名注射吸毒者在感染前、感染期间及感染后的情况，研究了急性感染后抗体反应的特异性、滴度及中和潜力。
血清转化定义为使用市售酶联免疫吸附测定（ELISA）法首次检测到HCV特异性抗体。在ELISA中使用重组抗原来测量HCV蛋白特异性抗体反应。对于中和试验，将血浆与人免疫缺陷病毒（HIV）-HCV H77或对照HIV-鼠白血病病毒（MLV）假型病毒孵育，然后使其感染Hep3B肝癌细胞。
HCV血清转化的平均时间为病毒血症开始后6周。在对结构蛋白的反应之前检测到对非结构蛋白的抗体反应，且两者的抗体主要局限于免疫球蛋白G1（IgG1）亚类。对结构蛋白和非结构蛋白的抗体反应的最大中位终点滴度分别为1:600和1:6400。仅在1名受试者血清转化时及3名受试者血清转化后6 - 8个月检测到中和带有HCV 1a包膜糖蛋白的逆转录病毒假型的抗体。中和抗体出现延迟与病毒包膜糖蛋白特异性抗体的后期产生一致，据信这些抗体介导病毒中和。
对急性HCV感染的体液免疫反应滴度相对较低，主要局限于IgG1亚类，且出现延迟。更好地理解中和抗体产生延迟的原因可能会改善预防HCV感染的努力。
