Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice.

Abstract

BACKGROUND & AIMS:

Hepatitis C virus (HCV) infection is a major cause of liver cancer, so strategies to prevent infection are needed. A system for cell culture of infectious HCV particles (HCVcc) has recently been established; the inactivated HCVcc particles might be used as antigens in vaccine development. We aimed to confirm the potential of HCVcc as an HCV particle vaccine.

METHODS:

HCVcc derived from the J6/JFH-1 chimeric genome was purified from cultured cells by ultrafiltration and ultracentrifugation purification steps. Purified HCV particles were inactivated and injected into female BALB/c mice with adjuvant. Sera from immunized mice were collected and their ability to neutralize HCV was examined in naive Huh7.5.1 cells and urokinase-type plasminogen activator-severe combined immunodeficiency mice (uPA(+/+)-SCID mice) given transplants of human hepatocytes (humanized livers).

RESULTS:

Antibodies against HCV envelope proteins were detected in the sera of immunized mice; these sera inhibited infection of cultured cells with HCV genotypes 1a, 1b, and 2a. Immunoglobulin G purified from the sera of HCV-particle-immunized mice (iHCV-IgG) inhibited HCV infection of cultured cells. Injection of IgG from the immunized mice into uPA(+/+)-SCID mice with humanized livers prevented infection with the minimum infectious dose of HCV.

CONCLUSIONS:

Inactivated HCV particles derived from cultured cells protect chimeric liver uPA(+/+)-SCID mice against HCV infection, and might be used in the development of a prophylactic vaccine.

• Authors: Daisuke Akazawa, Masaki Moriyama, Hiroshi Yokokawa, Noriaki Omi, Noriyuki Watanabe, Tomoko Date, Kenichi Morikawa, Hideki Aizaki, Koji Ishii, Takanobu Kato, Hidenori Mochizuki, Noriko Nakamura, Takaji Wakita
• Journal: Gastroenterology (Gastroenterology) Vol. 145 Issue 2 Pg. 447-55.e1-4 (Aug 2013) ISSN: 1528-0012 [Electronic] United States
• PMID: 23673355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Neutralizing
• Hepatitis C Antibodies
• Vaccines, Inactivated
• Viral Envelope Proteins
• Viral Hepatitis Vaccines

Topics

• Animals
• Antibodies, Neutralizing (immunology)
• Cell Culture Techniques
• Drug Design
• Female
• Hepacivirus
• Hepatitis C (prevention & control)
• Hepatitis C Antibodies (immunology)
• Hepatocytes (immunology)
• Humans
• Immunization
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Vaccines, Inactivated
• Viral Envelope Proteins (immunology)
• Viral Hepatitis Vaccines (immunology)
• Virion (immunology)