Codelivery of PEG-IFN-α inhibits HCV DNA vaccine-induced T cell responses but not humoral responses in African green monkeys

Park, Su–Hyung; Lee, Sang Rae; Hyun, Byung Hwa; Kim, Byong-Moon; Sung, Young Chul

doi:10.1016/j.vaccine.2008.05.017

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…Additionally, no significant T cell responses specific for HCV peptide pools were detected in HCV multigenic DNA-immunized group (group 1) even after the second vaccination. This observation is consistent with previous reports that, in contrast to small animals such as mice, twice vaccination with DNA is unlikely to induce antibody and T cell immune responses in non-human primates (29). However, these HCV-specific T cell responses became detectable after the third vaccination and then continuously increased by repeated DNA vaccination until the sixth vaccination.…”

Section: Resultssupporting

confidence: 93%

Codelivery of IL-7 Augments Multigenic HCV DNA Vaccine-induced Antibody as well as Broad T Cell Responses in Cynomolgus Monkeys

et al. 2010

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BackgroundA crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans.MethodsHere, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine.ResultsCodelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes.ConclusionTaken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.

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Section: Resultssupporting

confidence: 93%

Codelivery of IL-7 Augments Multigenic HCV DNA Vaccine-induced Antibody as well as Broad T Cell Responses in Cynomolgus Monkeys

et al. 2010

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“…4). Similarly, co‐delivery of IFN‐α to an HCV‐DNA vaccine 8, and treatment with IFN‐α before immunization with Mycobacterium tuberculosis reduces antigen‐specific proliferation 42, indicating that the presence of IFN‐α at the time of antigen sensitization may downregulate subsequent proliferation induced by antigenic re‐challenge. In contrast, the amelioration of arthritis in WT, as opposed to IFNAR KO mice (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…In vaccine studies, e.g. both an enhancing 7 and a clear dampening effect 8 of type I IFN signalling on the antigen‐specific immune response has been reported. Similarly, in experimental models of autoimmunity, type I IFN may either aggravate 9, 10 or mitigate 11–13 inflammation.…”

Section: Introductionmentioning

confidence: 99%

Type I IFN protects against antigen‐induced arthritis

Fei¹,

Chalise

Narendra

et al. 2011

Eur J Immunol

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Autoimmune diseases including rheumatoid arthritis (RA) involve immune reactions against specific antigens. The type I IFN system is suspected to promote autoimmunity in systemic lupus erythematosus, but may also dampen immune reactions in e.g. inflammatory bowel disease. This prompted us to investigate the role of type I IFN in antigeninduced arthritis (AIA). The importance of type I IFN in methylated (m) BSA-induced arthritis was studied by using mice deficient for the type I IFN receptor (IFNAR) and by administration of the IFN-a activator viral double-stranded (ds) RNA or recombinant IFN-a at antigen sensitization. In IFNAR knock-out mice, arthritis severity was significantly higher than in WT mice. Administration of dsRNA at antigen sensitization protected WT but not IFNAR KO mice from arthritis. Also, addition of recombinant IFN-a during the immunization, but not the induction phase of arthritis, almost abolished arthritis. Protection mediated by IFN-a was accompanied by delayed and decreased antigen-specific proliferative responses, including impaired lymph node recall responses after intraarticular antigenic challenge.In conclusion, we demonstrate that type I IFN can prevent joint inflammation by downregulating antigen-specific cellular immunity.Keywords: Arthritis . Tolerance . Type I IFN IntroductionThe cause of autoimmunity remains unknown, but a better understanding of what determines whether encounter with an antigen results in immunological attack or tolerance should provide strategies for deviating an existing autoimmune response. The type I IFNs, initially discovered for their direct anti-viral activity [1], are pluripotent cytokines with bearing also on adaptive immune responses [2], especially humoral immunity [3]. The rapid onset of type I IFN production in response to viral infection has suggested type I IFNs as potential instigators of viral-induced autoimmunity [4], although the link is only circumstantial. Interestingly, a number of auto-antibody related diseases, in particular systemic lupus erythematosus are characterized by a type I IFN signature, i.e. elevated levels of type I IFNs and products regulated by type I IFNs [5]. This may represent pro-inflammatory properties of type I IFN on adaptive, humoral immune responses, which may contribute to autoimmunity [6]. However, the effects of type I IFNs on antigen-specific immunity cannot be clearly categorized as either pro-or antiinflammatory. In vaccine studies, e.g. both an enhancing [7] and a clear dampening effect [8] of type I IFN signalling on the antigen-specific immune response has been reported. Similarly, in experimental models of autoimmunity, type I IFN may either aggravate [9,10] or mitigate [11][12][13] inflammation. The underlying mechanism(s) explaining these apparent contradictory findings remain to be determined. In arthritis, viral infections are known to exacerbate or precipitate inflammation [14], and viral interferogenic double-stranded (ds)RNA and IFN-a can be found at the site of inflammation in rheumatoid arthriti...

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“…CD8+ T cells could be eliminated against NS3/4A expressing hepatocytes and tumor cells in mouse model. No side effect was observed and two patients had viral load reductions of up to 1.2 and 2.4 log10 and the development of HCV-specific T cell reported (Ma et al, 2002;O'Hagan et al, 2004;Park et al, 2008;Memarnejadian and Roohvand, 2010).…”

Section: Dna Vaccinesmentioning

confidence: 93%

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

Keyvani

Fazlalipour²,

Monavari³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Codelivery of PEG-IFN-α inhibits HCV DNA vaccine-induced T cell responses but not humoral responses in African green monkeys

Cited by 9 publications

References 34 publications

Codelivery of IL-7 Augments Multigenic HCV DNA Vaccine-induced Antibody as well as Broad T Cell Responses in Cynomolgus Monkeys

Codelivery of IL-7 Augments Multigenic HCV DNA Vaccine-induced Antibody as well as Broad T Cell Responses in Cynomolgus Monkeys

Type I IFN protects against antigen‐induced arthritis

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

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