Synthetic antigens representing the antigenic variation of human hepatitis C virus.
Immune responses against hepatitis C virus (HCV) have been studied by numerous groups. However, details concerning the production of antibodies to antigenically variable epitopes remain to be elucidated. Since the sequences of the variable regions of several HCV proteins are different among the virus strains infecting patients, we decided to design peptide combinations that represent the theoretical maximum antigenic variation of each epitope to be used as capture antigens. We prepared six peptide mixtures (hypervariable epitope constructs; HECs) representing six different epitopes from structural and non-structural proteins of HCV from genotypes 1-6. Plasma from 300 HCV patients was tested to determine if their antibodies recognize the synthetic constructs. All the patients were chronically infected with diverse HCV genotypes and did not receive antiviral treatment. Antibodies to one or more of the HECs were detected in all of the HCV-infected individuals. Immunogenicity of the HCV HECs was also evaluated in outbred and inbred mice. Strong HEC-specific antibodies were produced, and cellular responses were also induced that were Th-1 rather than Th-2. Our results show that HCV HECs are both antigens that can be used to detect the broad cross-reactivity of antibodies from HCV-infected patients, and strong immunogens that can induce antigen-specific humoral and cellular immune responses in mice.
Kang
Kyung Hee
KH
Department of Medical Microbiology and Immunology, School of Medicine, University of California-Davis, Davis, California 95616, USA.
Yamamura
Yasuhiro
Y
Carlos
Maria P
MP
Karvelas
Nicolas
N
Kim
In-Sup
IS
Sunkara
Deepa
D
Rivera
Rebecca
R
Gardner
Murray B
MB
Anderson
David E
DE
Diaz-Mitoma
Francisco
F
Torres
José
J
Marquez
Juan P
JP
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D015678:Viral Structural Proteins