Hepatitis C Virus E2 Protein Purified from Mammalian Cells Is Frequently Recognized by E2-specific Antibodies in Patient Sera

Lee, Ki Jeong; Suh, Young‐Ah; Cho, Young Gyu; Cho, Young Shik; Ha, Gun Woo; Chung, Kwang-Hoe; Hwang, Jae-Hoon; Yun, Young Dae; Lee, Dong Hoon; Kim, Chang Min; Sung, Young‐Chul

doi:10.1074/jbc.272.48.30040

Cited by 20 publications

(34 citation statements)

References 38 publications

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“…It was of interest to determine how the truncation of E2 TMD decreased IFN-␥ ELISPOT responses for E2. Depending on the presence or absence of TMD, a major portion of E2 protein is either cell associated or secreted into the extracellular space (8,26). One explanation may be the different efficiencies of E2 and TMD-truncated E2 proteins (E2t) in cross-presentation.…”

Section: Discussionmentioning

confidence: 99%

Optimal Induction of T-Cell Responses against Hepatitis C Virus E2 by Antigen Engineering in DNA Immunization

Youn

Park

Cho

et al. 2003

J Virol

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Section: Discussionmentioning

confidence: 99%

Optimal Induction of T-Cell Responses against Hepatitis C Virus E2 by Antigen Engineering in DNA Immunization

Youn

Park

Cho

et al. 2003

J Virol

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“…Serum samples were diluted 1:50 and used for the determination of HCV-specific immunoglobulin G (IgG) responses by standard ELISA technique as described. 19,20 Plates were coated with 50 L (8 g/mL) of each protein (core, 1-191 aa); hgh-E1t, 192-383 aa; hghE2t, 384-718 aa; GST-NS3, 1205-1615 aa; MBP-NS4, 1637-1771 aa; or NS5, 2026-2339 aa) derived from gHCV strain. For semi-quantitative determination of E2-specific antibody responses, endpoint titration of antibodies was performed with two-fold serial dilutions.…”

Section: Methodsmentioning

confidence: 99%

Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee†

et al. 2005

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A t least 170 million people worldwide are persistently infected with hepatitis C virus (HCV), which is the most common reason for liver transplantation. An estimated 2.3 to 4.7 million people become newly infected every year, but an effective vaccine is not yet available. 1,2 Six different genotypes and a variety of quasispecies of HCV pose a major challenge for the development of an effective HCV vaccine. At present the chimpanzee is the only reliable experimental animal model in which to investigate the early events after HCV infection and to evaluate the efficacy of vaccine candidates. Since HCV-specific T-cell immunity has been known to be important in the control of HCV infection, 3-5 a substantial effort has been focused on the induction of vigorous HCV-specific T-cell immunity. Although a neutralizing antibody was considered to be crucial for vaccine-mediated protection against initial virus infection by blunting the infection at an early stage, 6 there have been few reports demonstrating the role of the antibody in the prevention of HCV infection. Vaccination with recombinant E1/E2 proteins in chimpanzees, albeit transient, induced strong antibody responses that were responsible for the prevention of a low dose of ho-

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“…The DNA vaccine vector pTV2sE2t was constructed to encode HCV E2 sequences (amino acid [aa] residues 384 to 719) of type 1b (Korean isolate) (19) fused to the herpes simplex virus type 1 glycoprotein D (gD) signal sequence (aa residues 1 to 34) (20). To obtain recombinant herpes simplex virus type 1 gD and HCV E2 proteins, stable Chinese hamster ovary (CHO) cell lines expressing gD and gDE2t were constructed.…”

mentioning

confidence: 99%

Enhancement of Immunoglobulin G2a and Cytotoxic T-Lymphocyte Responses by a Booster Immunization with Recombinant Hepatitis C Virus E2 Protein in E2 DNA-Primed Mice

Song¹,

Lee²,

Suh³

et al. 2000

J Virol

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The induction of strong cytotoxic T-lymphocyte (CTL) and humoral responses appear to be essential for the elimination of persistently infecting viruses, such as hepatitis C virus (HCV). Here, we tested several vaccine regimens and demonstrate that a combined vaccine regimen, consisting of HCV E2 DNA priming and boosting with recombinant E2 protein, induces the strongest immune responses to HCV E2 protein. This combined vaccine regimen augments E2-specific immunoglobulin G2a (IgG2a) and CD8؉ CTL responses to a greater extent than immunizations with recombinant E2 protein and E2 DNA alone, respectively. In addition, the data showed that a protein boost following one DNA priming was also effective, but much less so than those following two DNA primings. These data indicate that sufficient DNA priming is essential for the enhancement of DNA encoded antigen-specific immunity by a booster immunization with recombinant E2 protein. Hepatitis C virus (HCV) is a major causative agent of non-A, non-B hepatitis (7,18). Previous studies indicate that the development of chronic liver disease and hepatocellular carcinoma is closely associated with persistent infection of HCV (30). Currently, the lack of efficient antiviral treatment against HCV makes the development of a vaccine highly desirable. It is unclear which type of immunity is essential for HCV resolution. Recombinant protein vaccination facilitates strong antibody responses and stimulates primarily Th2 cells, which are defined by their secretion of the cytokines interleukin-4 (IL-4), IL-5, and IL-10. Protein vaccination with HCV envelope glycoproteins E1 and E2 induced protective immunity against homologous virus challenge in chimpanzees (8). In this model, the protection appeared to be correlated to the titers of anti-E2 antibodies, suggesting that antibody responses are important for protection against HCV infection. Furthermore, there are growing evidences that Th1 and cytotoxic Tlymphocyte (CTL) responses to HCV proteins may play a key role in virus resolution during natural infection (9,11,24,28). It has been reported that the prevalent cytokine pattern of circulating HCV-specific CD4 ϩ T cells is Th1-like in patients who recovered from acute hepatitis, as exhibited by the secretion of IL-2 and gamma interferon (11). In addition, chimpanzees which generated high levels of CTL responses to HCV proteins eliminated HCV infection (9). Thus, an effective HCV vaccine must elicit both strong humoral and cell-mediated immune responses, especially Th1 and CTL responses.Since it has been documented that DNA immunization preferentially induces Th1 immunity and CTL responses to many viral antigens (5, 26, 36), DNA vaccine approaches have been applied to generate protective immunity to a variety of pathogens (10, 12, 33). However, DNA immunization was also demonstrated to generate weaker antibody and CTL responses than did protein and live attenuated vaccinations, respectively (22, 32). In general, immunity generated by DNA vaccination alone appeared to be sufficient to prot...

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Hepatitis C Virus E2 Protein Purified from Mammalian Cells Is Frequently Recognized by E2-specific Antibodies in Patient Sera

Cited by 20 publications

References 38 publications

Optimal Induction of T-Cell Responses against Hepatitis C Virus E2 by Antigen Engineering in DNA Immunization

Optimal Induction of T-Cell Responses against Hepatitis C Virus E2 by Antigen Engineering in DNA Immunization

Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee†

Enhancement of Immunoglobulin G2a and Cytotoxic T-Lymphocyte Responses by a Booster Immunization with Recombinant Hepatitis C Virus E2 Protein in E2 DNA-Primed Mice

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