A. Zibert et al., EARLY ANTIBODY-RESPONSE AGAINST HYPERVARIABLE REGION-1 IS ASSOCIATED WITH ACUTE SELF-LIMITING INFECTIONS OF HEPATITIS-C VIRUS, Hepatology, 25(5), 1997, pp. 1245-1249
Antibodies directed to hypervariable region 1 (HVR1) of hepatitis C vi
rus (HCV) have recently been shown to neutralize the corresponding HCV
isolate in vitro. We analyzed the appearance of antibodies directed t
o HVR1 during the course of infection in a large group of patients who
have been infected by the same isolate of a HCV contaminated anti-D i
mmunoglobulin (HCV-AD78). An enzyme-linked immunosorbent assay (ELISA)
was established using a synthetic peptide to detect antibodies agains
t the main HVR1 variant of HCV-AD78. 207 sera obtained at different ti
me points post infection (p.i.) of 51 patients having either acute sel
f-limiting (n = 28) or chronic infection (n = 23) were studied. Antibo
dies directed to HVR1 were found at least at one time point during the
infection course in 15 of 28 patients (53%) having acute self-limitin
g infections and in 17 of 23 patients (74%) with chronic disease, The
time of appearance of anti-HVR1 was significantly different between th
ese two patient groups (P < .025) although appearance and titers of ot
her HCV-specific antibodies were found to be similar at early time poi
nts p.i. In acute self-limiting infections 9 of 21 sera (43%) of respe
ctive patients with sera available within the first 6 months p.i. were
anti-HVR1 positive. The highest prevalence of anti-HVR1 in this group
of patients was within month 6 to 12 p.i. (64%). None of the sera ava
ilable after 24 months p.i. had such antibodies, In contrast, only 2 o
f 15 sera (13%) of chronically infected patients with respective time
points of sera were anti-HVR1 positive within the first 6 months p.i.
and only 5 of 18 sera (28%) were positive within month 7 to 12 p.i. Se
ven patients with chronic HCV infections showed at least two consecuti
ve anti-HVR1 negative early time points up to month 18 p.i. Prevalence
of anti-HVR1 after 24 months p.i. was high (84%) in this group of pat
ients and most of the patients maintained high levels of anti-HVR1 for
up to 17 years p.i. Our findings suggest clearance of virus by respec
tive neutralizing antibodies resulting in a self-limiting infection an
d may have implications for prognosis of the disease and also for any
future vaccine development.