Prevention of Hepatitis C Virus Infection in Chimpanzees by Hyperimmune Serum Against the Hypervariable Region 1 of the Envelope 2 Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 Dec 24

PMID 8986822

Citations 220

Authors

P Farci

A Shimoda

D Wong

T Cabezon

D De Gioannis

A Strazzera

Y Shimizu

M Shapiro

H J Alter

R H Purcell

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Generation of Optimized Consensus Sequences for Hepatitis C virus (HCV) Envelope 2 Glycoprotein (E2) by a Modified Algorithm: Implication for a Pan-genomic HCV Vaccine.

Mohabati R, Rezaei R, Mohajel N, Ranjbar M, Samimi-Rad K, Azadmanesh K Avicenna J Med Biotechnol. 2024; 16(4):268-278.

PMID: 39606685 PMC: 11589427. DOI: 10.18502/ajmb.v16i4.16743.

Update on Hepatitis C Vaccine: Results and Challenges.

Garbuglia A, Pauciullo S, Zulian V, Del Porto P Viruses. 2024; 16(8).

PMID: 39205311 PMC: 11359353. DOI: 10.3390/v16081337.

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.

Pierce B, Felbinger N, Metcalf M, Toth E, Ofek G, Fuerst T Viruses. 2024; 16(5).

PMID: 38793684 PMC: 11125608. DOI: 10.3390/v16050803.

Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.

Mosa A, Campo D, Khudyakov Y, AbouHaidar M, Gehring A, Zahoor A Proc Natl Acad Sci U S A. 2023; 120(24):e2220294120.

PMID: 37276424 PMC: 10268328. DOI: 10.1073/pnas.2220294120.

Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies.

Gomez-Escobar E, Roingeard P, Beaumont E Viruses. 2023; 15(5).

PMID: 37243237 PMC: 10220683. DOI: 10.3390/v15051151.

References

Bellentani S, Tiribelli C, Saccoccio G, Sodde M, Fratti N, De Martin C . Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. Hepatology. 1994; 20(6):1442-9. DOI: 10.1002/hep.1840200611. View

Letvin N . Vaccines against human immunodeficiency virus--progress and prospects. N Engl J Med. 1993; 329(19):1400-5. DOI: 10.1056/NEJM199311043291908. View

Choo Q, Kuo G, Ralston R, Weiner A, Chien D, Van Nest G . Vaccination of chimpanzees against infection by the hepatitis C virus. Proc Natl Acad Sci U S A. 1994; 91(4):1294-8. PMC: 43144. DOI: 10.1073/pnas.91.4.1294. View

Rosa D, Campagnoli S, Moretto C, Guenzi E, Cousens L, Chin M . A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. Proc Natl Acad Sci U S A. 1996; 93(5):1759-63. PMC: 39854. DOI: 10.1073/pnas.93.5.1759. View

Kiyosawa K, Tanaka E, Sodeyama T, Furuta S . Natural history of hepatitis C. Intervirology. 1994; 37(2):101-7. DOI: 10.1159/000150363. View

Feinstone S, Alter H, Dienes H, Shimizu Y, Popper H, Blackmore D . Non-A, non-B hepatitis in chimpanzees and marmosets. J Infect Dis. 1981; 144(6):588-98. DOI: 10.1093/infdis/144.6.588. View

Taniguchi S, Okamoto H, Sakamoto M, Kojima M, Tsuda F, Tanaka T . A structurally flexible and antigenically variable N-terminal domain of the hepatitis C virus E2/NS1 protein: implication for an escape from antibody. Virology. 1993; 195(1):297-301. DOI: 10.1006/viro.1993.1378. View

Lesniewski R, Boardway K, Casey J, Desai S, Devare S, Leung T . Hypervariable 5'-terminus of hepatitis C virus E2/NS1 encodes antigenically distinct variants. J Med Virol. 1993; 40(2):150-6. DOI: 10.1002/jmv.1890400213. View

Bukh J, Miller R, Purcell R . Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis. 1995; 15(1):41-63. DOI: 10.1055/s-2007-1007262. View

10.

Kumar U, MONJARDINO J, Thomas H . Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient. Gastroenterology. 1994; 106(4):1072-5. DOI: 10.1016/0016-5085(94)90770-6. View

11.

Martell M, Esteban J, Quer J, Genesca J, Weiner A, Esteban R . Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol. 1992; 66(5):3225-9. PMC: 241092. DOI: 10.1128/JVI.66.5.3225-3229.1992. View

12.

Weiner A, BRAUER M, Rosenblatt J, Richman K, Tung J, Crawford K . Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology. 1991; 180(2):842-8. DOI: 10.1016/0042-6822(91)90104-j. View

13.

Farci P, Alter H, Govindarajan S, Wong D, Engle R, Lesniewski R . Lack of protective immunity against reinfection with hepatitis C virus. Science. 1992; 258(5079):135-40. DOI: 10.1126/science.1279801. View

14.

Hijikata M, Kato N, Ootsuyama Y, Nakagawa M, Ohkoshi S, Shimotohno K . Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochem Biophys Res Commun. 1991; 175(1):220-8. DOI: 10.1016/s0006-291x(05)81223-9. View

15.

Sekiya H, Kato N, Ootsuyama Y, Nakazawa T, Yamauchi K, Shimotohno K . Genetic alterations of the putative envelope proteins encoding region of the hepatitis C virus in the progression to relapsed phase from acute hepatitis: humoral immune response to hypervariable region 1. Int J Cancer. 1994; 57(5):664-70. DOI: 10.1002/ijc.2910570509. View

16.

Higashi Y, Kakumu S, Yoshioka K, Wakita T, Mizokami M, Ohba K . Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo. Virology. 1993; 197(2):659-68. DOI: 10.1006/viro.1993.1641. View

17.

Kato N, Sekiya H, Ootsuyama Y, Nakazawa T, Hijikata M, Ohkoshi S . Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus. J Virol. 1993; 67(7):3923-30. PMC: 237759. DOI: 10.1128/JVI.67.7.3923-3930.1993. View

18.

Farci P, Alter H, Wong D, Miller R, Shih J, Jett B . A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med. 1991; 325(2):98-104. DOI: 10.1056/NEJM199107113250205. View

19.

Okamoto H, Kojima M, Okada S, Yoshizawa H, Iizuka H, Tanaka T . Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: variability and stability. Virology. 1992; 190(2):894-9. DOI: 10.1016/0042-6822(92)90933-g. View

20.

Okamoto H, Mishiro S, Tokita H, Tsuda F, Miyakawa Y, Mayumi M . Superinfection of chimpanzees carrying hepatitis C virus of genotype II/1b with that of genotype III/2a or I/1a. Hepatology. 1994; 20(5):1131-6. View