Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates

Capone, Stefania; Zampaglione, Immacolata; Vitelli, Alessandra; Pezzanera, Monica; Kierstead, Lisa; Burns, Janine; Ruggeri, Lionello; Arcuri, Mirko; Cappelletti, Manuela; Meola, Annalisa; Ercole, Bruno Bruni; Tafi, Rosalba; Santini, Claudia; Luzzago, Alessandra; Fu, Tong-Ming; Colloca, Stefano; Ciliberto, Gennaro; Cortese, Riccardo; Nicosia, Alfredo; Fattori, Elena; Folgori, Antonella

doi:10.4049/jimmunol.177.10.7462

Cited by 78 publications

(43 citation statements)

References 50 publications

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“…Others showed that a DNA vaccine encoding an optimized version of the nonstructural region of hepatitis C virus delivered by EP induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than IM DNA injection in mice and in rhesus macaques [31]. Thus, epitope mapping studies are needed to address this issue.…”

Section: Discussionmentioning

confidence: 99%

Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques

Hirao

Khan³

et al. 2008

Vaccine

133

117

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DNA vaccines are a promising technology. Historically, however, the ability of DNA vaccines to induce high response rates and strong immune responses, especially antibody responses, in nonhuman primates and human clinical trials has proven suboptimal. Here, we performed a pilot study in rhesus macaques to evaluate whether we could improve the immunogenicity of DNA vaccines through the use of adjuvant technology and improved delivery systems. The study consisted of four groups of animals that received: DNA by intramuscular (IM) injection, DNA with plasmidencoded IL-12 by IM injection, DNA by IM injection with in vivo electroporation (EP), and DNA with IL-12 by IM EP. Each group was immunized three times with optimized HIV gag and env constructs. Vaccine immunogenicity was assessed by IFNγ ELISpot, CFSE proliferation, polyfunctional flow cytometry, and antibody ELISA. Similar to previous studies, use of IL-12 as an adjuvant increased the gag and env-specific cellular responses. The use of EP to enhance plasmid delivery resulted in dramatically higher cellular as well as humoral responses. Interestingly, the use of EP to administer the DNA and IL-12 adjuvant combination resulted in the induction of higher, more efficient responses such that a 10 fold increase in antigen-specific IFNγ + cells compared to IM DNA immunization was observed after a single immunization. In addition to increases in the magnitude of IFNγ production in the initial and memory responses, the combined approach resulted in enhancements in the proliferative capacity of antigen-specific CD8 + T cells and the amount of polyfunctional cells capable of producing IL-2 and TNFα in addition to IFNγ. These data suggest that adjuvant and improved delivery methods may be able to overcome previous immunogenicity limitations in DNA vaccine technology.

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Section: Discussionmentioning

confidence: 99%

Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques

Hirao

Khan³

et al. 2008

Vaccine

133

117

View full text Add to dashboard Cite

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“…For instance, recent reports have shown that EP can induce reactivity against a broader range of epitopes than conventional vaccine administration. Thus far, this has been demonstrated only with T cell epitopes [7][8][9]. If this is also the case for B cell epitopes, this could include epitopes that are critical for neutralizing activity.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is thought that methods for enhancing intracellular delivery of DNA vaccines could improve immunogenicity and enable the technology for clinical use [4]. In that regard, electroporation (EP) appears promising, because it is a potent in vivo method for intracellular gene delivery [5] as well as a very effective means for DNA vaccination [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Potentiation of an anthrax DNA vaccine with electroporation

Luxembourg¹,

Hannaman²,

Nolan³

et al. 2008

Vaccine

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“…We therefore suggest that electroporationadjuvant strategies may have better efficacy in increasing the expression level of DNA vaccines in human applications, which are consistent with the previous reported results. 44,45 However, the electroporation can also induce cytokine secretion and inflammatory cell infiltration in the muscle hours after the treatment, 46,47 which may also facilitate SAP-mediated clearance and limits the efficacy of DNA vaccines. We therefore suggest that electroporation should be preformed immediately after DNA inoculation.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

et al. 2011

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The demonstration that naked plasmid DNA can induce strong immune responses in mice has attracted considerable attention in the vaccine community. However, similar immunizations have been less/not effective in clinical trials during the past decade, and the underlying mechanisms remain unknown. In this study, we hypothesized that some DNA-binding proteins in human serum may serve as host barriers, responsible for the low efficiency of plasmids' transfection in vivo. Using proteomics, we showed that human serum amyloid P component (hSAP) is specifically present in human DNA-protein complexes. Further analysis indicated that hSAP effectively binds plasmid DNA, inhibits DNA transfection into somatic cells and facilitates the endocytosis of DNA by macrophages, whereas mouse SAP (mSAP) has similar, but much weaker, activities. In the presence of hSAP, the plasmid DNA expression in vivo and plasmid DNA-induced immune responses also significantly decreased. Therefore, our results suggest that hSAP contributes to extracellular DNA clearance and the inhibition of plasmid DNA transfection in vivo. This mechanism may be partly responsible for the insufficient immune responses to DNA vaccination in human beings; therefore, it may serve as a novel target for the improvement of DNA vaccines and DNA-based gene therapy.

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Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates

Cited by 78 publications

References 50 publications

Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques

Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques

Potentiation of an anthrax DNA vaccine with electroporation

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

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