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

Youn, Jin-Won; Park, Su–Hyung; Cho, Jaeho; Sung, Young Chul

doi:10.1128/jvi.77.21.11596-11602.2003

Cited by 23 publications

(11 citation statements)

References 44 publications

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“…In this case, wild‐type E7 antigen failed to show any protection from tumour challenge. Our observation is in line with previous findings in the HSV‐2 gD and HCV E2 DNA vaccination model systems 20,21 , 37 . In HSV‐2 gD studies, deletion of the TMR sequence from gD antigens resulted in enhanced protective immunity against HSV‐2 challenge, as opposed to wild‐type gD antigens (membrane‐targeted form) while deletion of both signal and TMR sequences generating a cytosolic gD form showed little protective immunity.…”

Section: Discussionsupporting

confidence: 91%

Both antigen optimization and lysosomal targeting are required for enhanced anti‐tumour protective immunity in a human papillomavirus E7‐expressing animal tumour model

Kim¹,

Sin

2005

Immunology

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Summary DNA immunization is a new approach for cancer immune therapy. In this study, we constructed human papillomavirus (HPV) 16 E7 expression vector cassettes and then compared the abilities of these constructs to induce antitumour protection. Lysosome‐targeted E7 antigens, and to a lesser degree signal sequence‐conjugated and transmembrane region sequence‐conjugated E7 antigens in a DNA form, displayed tumour protection significantly higher than wild‐type E7 antigens. This enhanced tumour protection was mediated by CD8+ cytotoxic T lymphocytes (CTL), as determined by in vivo T‐cell depletion and in vitro interferon‐γ (IFN‐γ) production. Subsequent co‐injection with interleukin‐12‐expressing cDNA showed insignificantly enhanced antitumour protection. However, E7 codon optimization plus lysosomal targeting resulted in a dramatic enhancement in antitumour protection both prophylactically and therapeutically through augmentation of the E7‐specific CTL population, compared to either one of them alone. However, wild‐type or codonoptimized E7 antigens without intracellular targeting displayed no protection against tumour challenge. Thus, these data suggest that antigen codon optimization plus lysosomal targeting strategy could be important in crafting more efficacious E7 DNA vaccines for tumour protection.

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Section: Discussionsupporting

confidence: 91%

Both antigen optimization and lysosomal targeting are required for enhanced anti‐tumour protective immunity in a human papillomavirus E7‐expressing animal tumour model

Kim¹,

Sin

2005

Immunology

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“…10 pGX10-s⌬ST plasmid encodes structural genes, which are devoid of N-terminal 40 aa to abolish the immunosuppresive effect of core protein. 10,11 The murine interleukin 12 (IL-12) gene of pGX10-mIL-12N220L was replaced with the human IL-12N222L gene to generate pGX10-hIL-12N222L. 12-14 pGX10-hIL-12N222L was added to the DNA102 vaccine, and the product was named DNA103 vaccine.…”

Section: Methodsmentioning

confidence: 99%

“…A panel of a total of 93 overlapping peptides was synthesized by Peptron Inc. (Daejon, South Korea), to have 20 aa in length, with 10 aa overlap; 12 peptides for core (43-172 aa), 31 for E2 (384-713 aa), 16 for NS3 protease (1029-1217 aa), and 34 for NS3 helicase (1208-1647 aa). The peptide sequence was derived from the gHCV vaccine strain (genotype 1b), 10 and used for stimulation in the interferon gamma (IFN-␥) ELISPOT assay.…”

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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“…A vacinação com DNA contendo genes do vírus influenza (Bot et al, 1998;Ulmer et al, 1998), vírus do sarampo e vírus Sendai (Martinez et al, 1997), vírus da leucemia murina (Sarzotti et al, 1996), vírus da hepatite C (Youn et al, 2003), HIV (Asakura et al, 1999) mostrou-se eficaz em estabelecer a resposta imune antiviral em alguns modelos animais como os roedores. Em humanos, as vacinas de DNA não são tão eficazes, quando administradas como naked DNA pelas vias intramuscular ou intradérmica, entretanto têm mostrado resultados promissores quando combinadas com outras formas de vacina, como os vetores virais (Lu, Wang e Grimes-Serrano, 2008).…”

Section: Infectam (Unaids 2008)unclassified

Imunogenicidade da vacina de DNA quimérica LAMP-1/p55Gag do HIV-1 no período neonatal e efeito da imunização materna na resposta vacinal da prole de camundongos.

Rigato¹

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

Cited by 23 publications

References 44 publications

Both antigen optimization and lysosomal targeting are required for enhanced anti‐tumour protective immunity in a human papillomavirus E7‐expressing animal tumour model

Both antigen optimization and lysosomal targeting are required for enhanced anti‐tumour protective immunity in a human papillomavirus E7‐expressing animal tumour model

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

Imunogenicidade da vacina de DNA quimérica LAMP-1/p55Gag do HIV-1 no período neonatal e efeito da imunização materna na resposta vacinal da prole de camundongos.

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