Farci P, Shimoda A, Wong D, Cabezon T, De Gioannis D, Strazzera A, Shimizu Y, Shapiro M, Alter H J, Purcell R H
Hepatitis Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15394-9. doi: 10.1073/pnas.93.26.15394.
The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. Here, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV.
鉴定丙型肝炎病毒（HCV）的中和结构域对于开发有效的疫苗至关重要。在此，我们表明包膜2（E2）蛋白的高变区1（HVR1）是HCV的关键中和结构域。我们用针对源自E2蛋白HVR1的同源合成肽产生的兔超免疫血清尝试在体外中和HCV，并通过接种HCV血清阴性的黑猩猩来评估残余感染性。HCV的来源是从一名输血后非甲非乙型肝炎急性期患者（H）获得的血浆，该血浆已在黑猩猩中进行了感染性滴定。抗HVR1抗血清在黑猩猩中诱导了针对同源HCV感染的保护作用，但不能防止中和逃逸突变体的出现，这些突变体被发现已存在于接种物的复杂病毒准种中。HVR1可引发保护性免疫这一发现为开发有效的预防策略开辟了新的前景。然而，将HCV最可变的区域鉴定为关键中和结构域对开发针对HCV的广泛反应性疫苗构成了重大挑战。
