A DNA vaccine containing inverted terminal repeats from adeno‐associated virus increases immunity to HIV

Xin, Ke-Qin; Ooki, Takaaki; Jounai, Nao; Mizukami, Hiroaki; Hamajima, Kenji; Kojima, Yoshitsugu; Ohba, Kihachiro; Toda, Yoshihiko; Hirai, Syu-ichi; Klinman, Dennis M.; Ozawa, Keiya; Okuda, Kenji

doi:10.1002/jgm.356

Cited by 20 publications

(12 citation statements)

References 28 publications

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“…The inverted terminal repeat (ITR) sequences of the adeno-associated virus in plasmid DNA vaccine encoding HIV-1 Gag or Env under the control of CMV enhancer/promoter augment humoral and cellular immune responses [50,54]. This booster effect of the ITR sequences is thought to be associated with upregulation of transgene expression in mice because an addition of the ITR sequences to plasmid DNA increases transgene expression in cultured cells.…”

Section: Discussionmentioning

confidence: 99%

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

et al. 2007

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Accumulation of aggregated amyloid β-protein (Aβ) in the brain is thought to be the initiating event leading to neurodegenetation and dementia in Alzheimer's disease (AD). Therefore, therapeutic strategies that clear accumulated Aβ and/or prevent Aβ production and its aggregation are predicted to be effective against AD. Immunization of AD mouse models with synthetic Aβ prevented or reduced Aβ load in the brain and ameliorated their memory and learning deficits. The clinical trials of Aβ immunization elicited immune responses in only 20% of AD patients and caused T-lymphocyte meningoencephalitis in 6% of AD patients. In attempting to develop safer vaccines, we previously demonstrated that an adenovirus vector, AdPEDI-(Aβ1-6) 11 , which encodes 11 tandem repeats of Aβ1-6 can induce anti-inflammatory Th2 immune responses in mice. Here, we investigated whether a DNA prime-adenovirus boost regimen could elicit a more robust Th2 response using AdPEDI-(Aβ1-6) 11 and a DNA plasmid encoding the same antigen. All mice (n = 7) subjected to the DNA prime-adenovirus boost regimen were positive for anti-Aβ antibody, while, out of 7 mice immunized with only AdPEDI-(Aβ1-6) 11 , four mice developed anti-Aβ antibody. Anti-Aβ titers were indiscernible in mice (n = 7) vaccinated with only DNA plasmid. The mean anti-Aβ titer induced by the DNA prime-adenovirus boost regimen was approximately 7-fold greater than that by AdPEDI-(Aβ1-6) 11 alone. Furthermore, anti-Aβ antibodies induced by the DNA prime-adenovirus boost regimen were predominantly of the IgG1 isotype. These results indicate that the DNA primeadenovirus boost regimen can enhance Th2-biased responses with AdPEDI-(Aβ1-6) 11 in mice and suggest that heterologous prime-boost strategies may make AD immunotherapy more effective in reducing accumulated Aβ.

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Section: Discussionmentioning

confidence: 99%

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

et al. 2007

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“…This finding is consistent with the observations made in Breakefield's lab using HSV-1 amplicon vectors containing the AAV ITRs and many other reports using plasmids containing the AAV ITRs. [19][20][21][22][23][24][25][26][27][28] The AAV ITRs used in this study, however, appeared to be unable to change the dynamics of transgene expression. With or without the sequences, cultured cells and brain tissues transduced by the baculovirus vectors harboring the hybrid CMV enhancer/GFAP promoter displayed similar patterns of time-dependent decrease in gene expression.…”

Section: Gfap Promoter In Baculovirus Vectors Cy Wang and S Wangmentioning

confidence: 99%

“…9,11,17,18 Another reported approach useful to the improvement of transgene expression is flanking an expression cassette of interest with the inverted terminal repeats (ITRs) of AAV. Several groups have modified their viral or plasmid vectors with this approach and reported the improved efficiency of gene expression in mammalian cells, [19][20][21][22][23][24][25] Xenopus embryos 26 and fishes. 27,28 For this study, we constructed recombinant baculovirus vectors accommodating the GFAP promoter and set out to investigate whether the above two approaches, in particular when the CMV enhancer and the AAV ITRs were used together, could improve transgene expression in an astrocyte-specific manner.…”

Section: Introductionmentioning

confidence: 99%

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Wang

2006

Gene Ther

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Therapeutic gene expression in glial cells has been tested for the treatment of neurological diseases in animal models. Many of such studies used the promoter of the glial fibrillary acidic protein (GFAP) to restrict gene expression to astrocytes. We have investigated in the current study whether it is possible to improve the transcriptional activity of the cellular promoter, while maintaining its cell-type specificity. We constructed an expression cassette containing a hybrid cytomegalovirus (CMV) enhancer/GFAP promoter and placed it into baculovirus vectors, a type of viral vectors capable of transducing astrocytes. In another vector design, we used inverted terminal repeats (ITRs) from adeno-associated virus (AAV) to flank the expression cassette. The recombinant baculoviruses with the hybrid promoter improved gene expression levels over two orders of magnitude in glial cell lines and by 10-fold in the rat brain when compared to the baculoviruses with the GFAP promoter alone. The expression was further improved by ITR flanking, reaching levels higher than that mediated by the baculovirus vectors with the CMV immediate-early enhancer/ promoter (CMV promoter). Using these recombinant baculoviruses, we observed extended in vivo transgene expression in the rat brain at 90 days postinjection, by which time the gene expression from baculovirus vectors with the GFAP or CMV promoter had already become undetectable. The astrocyte specificity of the GFAP promoter was preserved in the engineered expression cassette with the CMV enhancer and the AAV ITRs, as demonstrated by immunohistological analysis of brain samples and an axonal retrograde transport assay. Taken together, our findings suggest that these baculovirus vectors may serve as useful tools for astrocyte-specific gene expression in the brain.

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“…ELISA was used for titration of IgG responses, as described elsewhere. 30 Briefly, 96-well plates were coated overnight at 4˚C with HIV-1 gp120 or gag/pol proteins clade B (NIH), and the wells were washed with PBS containing 0.05% Tween 20 and then blocked for 1 h with 1% BSA in PBS. The plates were incubated for 2 h at 37˚C with seriallydiluted sera.…”

Section: Methodsmentioning

confidence: 99%

Potency of Cell-Mediated Immune Responses to Different Combined HIV-1 Immunogens in a Humanized Murine Model

et al. 2005

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In this study, cell-mediated immune responses were evaluated in HLA-A2.1 mice that received polycistronic vector expressing HIV-1 gp120, gag and pol or single vectors expressing gp120 + gag/pol as well as recombinant structural proteins and adjuvants. Mice primed with the polycistronic DNA/CpG and boosted with the same regimen plus proteins induced a higher T-cell proliferative response to gp120. However, a very high frequency of IFN-γ was detected in mice receiving the mixture of gp120 + gag/pol DNA constructs, recombinant proteins and CpG. We also measured specific CD8 + T cells in PBMCs by intracellular cytokine and HLA-A2.1-peptide dimer staining in response to HLA-A2.1-restricted HIV-1 epitopes (gp120, gag and pol). The group that received single gp120 + gag/pol DNA constructs, recombinant proteins and CpG had a higher CD8 + T cell response to the combination of peptides compared to the other groups that received the polycistronic construct. The present study reveals an optimal combination of immunogens to enhance immune responses against HIV-1.

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A DNA vaccine containing inverted terminal repeats from adeno‐associated virus increases immunity to HIV

Abstract: AAV ITRs enhance CMV-dependent up-regulation of transgene expression and immunogenicity of DNA vaccine.

Cited by 20 publications

References 28 publications

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Potency of Cell-Mediated Immune Responses to Different Combined HIV-1 Immunogens in a Humanized Murine Model

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