Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

Fournillier, Anne; Nakano, Isao; Vitvitski, L.; Depla, Erik; Vidalin, Olivier; Maertens, Geert; Trépo, Christian; Inchauspé, Geneviève

doi:10.1002/hep.510280131

Cited by 27 publications

(17 citation statements)

References 46 publications

(62 reference statements)

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“…The following boundaries were used: for the core protein, amino acids (aa) 1 to 191 (pCMVC2) (41); for E1, aa 134 to 328 (pCIE1t); for E2, aa 340 to 674 (pCIE2t); and for NS3, aa 1027 to 1657 (pCINS3) (3). The assessment of antigen production was performed as described previously (16,17,41). The constructs were used for the immunization of mice and elicited strong humoral as well as cellular immune responses (3, 41; G. Inchauspé, unpublished data).…”

Section: Animalsmentioning

confidence: 99%

Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

Rollier

Depla

Drexhage

et al. 2004

J Virol

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The hepatitis C virus (HCV) is the etiologic agent of non-A non-B hepatitis, the leading cause of chronic liver infections. Chronic HCV infection is correlated with the risk of developing liver cirrhosis and hepatocellular carcinoma (1). It is estimated that there are more than 170 million chronic carriers worldwide (44). To date, there is neither a prophylactic vaccine nor a satisfactory therapeutic treatment (27), and although routine testing of blood products for HCV has reduced posttransfusion infection in the Western world, not all of the routes of transmission are known, and new cases are still accumulating.The development of an HCV vaccine has been problematic due to the logistics and the ethical restrictions in the numbers and use of chimpanzees, the only species other than Homo sapiens that is susceptible to chronic HCV infection. Furthermore, essential information regarding the immune correlates of protective immunity is still lacking. Although important proof-of-principle ex vivo neutralization studies have been undertaken with chimpanzees (14), neutralizing antibodies are not easily attained and are considered insufficient for viral clearance or the prevention of reinfection (9, 13). The study of immune responses induced in individuals and chimpanzees with acute resolved versus chronic infections has so far revealed only an emerging picture of potential protective immune responses following the establishment of active viral infection. In addition to innate host immunity (38), the importance of cytotoxic T lymphocytes (CTLs) (9,12,18,43,46), gamma interferon (IFN-␥)-producing T cells homing into the liver (36), and T-helper (Th) responses (4,10,20,26) in the control of HCV infection has been demonstrated. However, the correlates of prophylactic vaccine protection following parenteral immunization are expected to be largely extrahepatic prior to HCV exposure. We set out to correlate such peripheral immune responses with vaccine efficacy in order to identify peripheral immune readouts that are likely to be indicative of a desirable vaccine-induced response. Such end points should be readily measurable in human volunteers without necessitating invasive liver biopsies.A limited number of vaccine efficacy studies have been performed with chimpanzees. Immunization with E1 and E2 proteins protected five out of seven animals from infection after a low-dose homologous challenge (with exactly the same clone being used for immunization and challenge) (8) but not against heterologous challenge. In another study, DNA expressing E2 was used to immunize two chimpanzees. Following homologous challenge, both vaccinees became infected but resolved the infection (15). However, none of these studies provided insights into the nature of the vaccine-induced immune correlates of clearance. In addition, HCV presents a high degree of variability (35). Multiple genotypes coexist worldwide, and in * Corresponding author. Mailing address: UMR 2142 CNRS/BioMerieux, 46 allee d'Italie,

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Section: Animalsmentioning

confidence: 99%

Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

Rollier

Depla

Drexhage

et al. 2004

J Virol

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“…This suggests that Ab responses could be an important protective correlate for protection against HCV infection. Previously, DNA vaccines expressing HCV core, E1, and E2 proteins have been shown to induce Ag-specific Ab and Th cell proliferative responses, as well as CTL in animals (Lagging et al, 1995;Major et al, 1995;Encke et al, 1998;Fournillier et al, 1998). Moreover, gene gun delivery of DNA vaccine containing both a codon-optimized synthetic HCV NS3/4A sequence and Semliki forest virus replicon resulted in an improved immunogenicity as evidenced by higher levels of NS3-specific antibodies (Frelin et al, 2004).…”

Section: Hepatitis Virusmentioning

confidence: 99%

DNA Vaccines against Infectious Diseases and Cancer

Han¹,

Weiner²,

Sin³

2010

Biomolecules and Therapeutics

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-Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.

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“…Since E1 has been shown to be a poor immunogen in all studies reported so far [42,43], most of the gathered data are specific to E2-derived vaccines. Original studies have exploited different fusion contexts of the E2 protein in order to try and optimize its immunogenicity either by optimizing its capacity to be secreted or by favoring its expression on the cell surface.…”

Section: Induction Of E1-and E2-specific Immune Responsesmentioning

confidence: 99%

DNA Vaccines for Hepatitis C Virus

Brinster

Inchauspé²

2001

Intervirology

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Hepatitis C virus is an RNA encoded virus of the Flaviviridae family. In most cases, infections develop into a chronic carrier stage that can result in the onset of cirrhosis and hepatocellular carcinoma over a 20- to 30-year period. Because existing therapies are still of limited benefit and expensive, the development of a vaccine represents a priority to prevent further spreading of the infection. Immune correlates of protection remain poorly defined although increasing evidence suggests that both humoral and cellular immune responses are likely to contribute to protection and/or neutralization of the virus. Current DNA-based vaccines, while capable of generating the latter, appear limited in their capacity to induce a strong and long-lasting antibody response.

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Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA using single or combined delivery routes

Cited by 27 publications

References 46 publications

Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

Control of Heterologous Hepatitis C Virus Infection in Chimpanzees Is Associated with the Quality of Vaccine-Induced Peripheral T-Helper Immune Response

DNA Vaccines against Infectious Diseases and Cancer

DNA Vaccines for Hepatitis C Virus

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