Enhanced cell-mediated IFN-γ-secreting activity against the HIV-1IIIB V3 peptide of the TAB9 multiepitope after DNA vaccine backbone engineering

Rodríguez, Ernesto Galbán; Vázquez, Dania Marcia; Herrera, Antonieta M; Duarte, Carlos A.

doi:10.1016/s0006-291x(03)01462-1

Cited by 7 publications

(10 citation statements)

References 23 publications

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“…For the three different CpG-modified pSCAR DNA replicon vaccines, stronger humoral, cellular, and protective immune responses were also elicited in mice when compared with the control unmodified pSCAR groups. Our results are in contrast to those of previous studies in which the CpG motifs were shown to only increase cell-mediated immune responses [17][18][19] or antibody responses [7,16]. In some cases, the CpG motifs may even have no effect or an inhibitory effect on immunogenicity of DNA vaccines [8,9,29,30].…”

Section: Discussioncontrasting

confidence: 99%

“…Some studies as well as the present study showed that antigen-specific humoral and cellular immunity can be increased by CpG modification of DNA plasmids [9,20,21,30,32]. While other studies showed that only antigen-specific cellular immunity and not antibody responses can be increased for other antigens/pathogens [17][18][19]. Except that different profiles of β-Gal, AHc, or PA4-specific immune responses were elicited in the none-viral DNA plasmid vaccines, two types of DNA vectors encoding the AHc or PA4 also produced different immune responses and protective potencies.…”

Section: Discussionsupporting

confidence: 51%

“…Plasmid DNA containing CpG motifs or synthetic CpG oligonucleotides (CpG ODNs) triggers an immune response characterized by the activation of B cells, NK cells, and monocytes/macrophages to proliferate, mature, and secrete a variety of cytokines, chemokines, and/or immunoglobulins [11][12][13][14]. Based on evidence obtained in mice that DNA plasmids containing large numbers of CpG motifs can augment the immunogenicity of DNA vaccines, such modifications in the plasmid backbone has emerged as an alternate strategy for optimizing immune responses [7,8,10,[15][16][17][18][19][20][21]. The in vitro activities and chemical components of three major types of immunostimulatory CpG ODNs (A, B, or C type) are well characterized [13,14,22,23].…”

Section: Introductionmentioning

confidence: 99%

“…The in vitro activities and chemical components of three major types of immunostimulatory CpG ODNs (A, B, or C type) are well characterized [13,14,22,23]. However, several previous studies have used only one [17][18][19][20][21] or at most two types of CpG motifs [10] to modify the plasmid backbone. Little is known about the C type in this regard.…”

Section: Introductionmentioning

confidence: 99%

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Three types of humanCpG motifs differentially modulate and augment immunogenicity of nonviral and viral repliconDNA vaccines as built‐in adjuvants

Li²,

Ma³

et al. 2012

Eur J Immunol

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Naked DNA vaccines given by intramuscular injection are efficient in mouse models, but they require improvement for human use. As the immunogenicity of DNA vaccines depends, to a large extent, on the presence of CpG motifs as built-in adjuvants, we addressed this issue by inserting three types of human CpG motifs (A-type, B-type, and C-type) into the backbone of nonviral DNA and viral DNA replicon vectors with distinct immunostimulatory activities on human PBMCs. The adjuvant effects of CpG modifications in DNA vaccines expressing three types of antigens (β-Gal, AHc, or PA4) were then characterized in mice and found to significantly enhance antigen-specific humoral and cell-mediated immune responses. The three types of CpG motifs also differentially affected and modulated immune responses and protective potency against botulinum neurotoxin serotype A and Bacillus anthracis A16R challenge. Taken together, these results demonstrate that insertion of human CpG motifs can differentially modulate the immunogenicity of nonviral DNA vaccines as well as viral DNA replicon vaccines. Our study provides not only a better understanding of the in vivo activities of CpG motif adjuvants but implications for the rational design of such motifs as built-in adjuvants for DNA vectors targeting specific antigens.Keywords: adjuvant · CpG · DNA vaccine · Immunogenicity · Replicon vector Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPrevious studies have proved that DNA immunization can elicit antigen-specific humoral and cell-mediated immune responses and provide effective protective immunity against a variety of pathogens in various animal models [1,2]. However, the potency of naked DNA vaccines produced in nonhuman primates and humans is usually lower than that in the small animals used in these models [1]. Additionally, early DNA vaccines did not Correspondence: Dr. Zhi-Wei Sun e-mail: szwyhhh@yahoo.com.cn afford sufficient immunogenicity in human clinical studies. Therefore, the efficacy of DNA vaccines must be modulated and augmented to enable this technology to be successfully applied to human clinical trials. A number of strategies have been investigated to increase the immunogenicity of DNA vaccines over the last few years, including adjuvants, alterations in the codon bias, cytokines, chemokines, CpG, electroporation, liposomes, microparticles, and heterologous prime/boost immunization [2][3][4][5][6]. * These authors contributed equally to this work. The levels of IL-6 and IFN-γ in the culture supernatants of human PBMCs cultured with the indicated (C) CpG-modified nonviral DNA plasmids or (D) viral DNA replicon plasmids were determined by ELISA. Data are represented as mean + SD of n = 6 samples and are from one experiment representative of two experiments performed. Statistical significance over the control unmodified plasmids and media was determined by ANOVA test ( * P < 0.05; ** P < 0.01; *** P < 0.001).Previous studies have shown that the ef...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Three types of humanCpG motifs differentially modulate and augment immunogenicity of nonviral and viral repliconDNA vaccines as built‐in adjuvants

Li²,

Ma³

et al. 2012

Eur J Immunol

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“…The pMAE5D5 vector is a derivative of previously developed pMAE plasmids [18,21]. The expression cassette in pMAE5D5 has a synthetic chimeric intron composed of the 5¢-donor site from the first intron of the human b-globin gene and the branch and 3¢-acceptor site from the intron of an immunoglobulin heavy chain variable region, and the synthetic t/polyA based on the equivalent element of the rabbit b-globin gene.…”

Section: Plasmid Dna Vaccine Constructsmentioning

confidence: 99%

Prophylactic naked DNA vaccination with the human vascular endothelial growth factor induces an anti-tumor response in C57Bl/6 mice

et al. 2007

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Passive immunotherapy against soluble pro-angiogenic factors and/or their receptors in endothelial cells has become a promising approach in cancer therapeutics. There is also experimental evidence indicating that an active immunotherapy strategy directed towards these target molecules could also be effective. In this paper we show that it is possible to reduce tumor growth or increase the survival of tumor-bearing C57Bl/6 mice when animals are vaccinated with the human vascular endothelial growth factor (VEGF) isoform 121 gene (hVEGF(121)), and later challenged with melanoma or lung carcinoma tumor cells. Immunization was done with 10 microg DNA doses of the hVEGF121 gene, which is highly homologous to its mouse counterpart, administered on a weekly basis using a plasmid bearing 5 CpG bacterial motifs. Histopathology analyses of tumors of hVEGF(121) immunized animals showed a decrease in tumor cell density around vessels and in mitotic figures, as well as an increase in apoptotic tumor cells. A statistically significant cell cytotoxic response was found when spleen cells of immunized mice were co-cultured in vitro with mouse tumor VEGF-producing cells. Vaccination with an hVEGF121 gene mutated to make it deficient for VEGF receptor binding, produced similar in vitro and in vivo results, and significantly reduced the number of spontaneous metastases produced by the mouse Lewis lung carcinoma. Our results indicate that human VEGF DNA can be employed for anti-angiogenic active immunotherapy in mice, and that direct cell cytotoxicity is a contributor mechanism to the overall anti-tumor effects seen in immunized animals.

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Nonviral DNA vectors for immunization and therapy: design and methods for their obtention

Rodríguez

2004

J Mol Med

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The use of plasmid DNA for vaccination and therapy is a relatively novel technology, with advantages and limitations as with other gene transfer techniques. The technology is based on DNA vectors designed for administering genes coding for relevant proteins into a given organism, fulfilling requirements of the regulatory agencies that once properly formulated and delivered the desired vaccine/therapeutic effect can be achieved. Starting from conventional plasmid DNA vectors currently tested in clinical trials, improvement resulted in bacterial element-less vectors, increasing the complexity of the developmental process. The present review focuses on systems described for generating these nonviral DNA vectors for immunization and therapy from bacterial hosts (conventional and conditionally replicating plasmids, nonreplicating minicircles, and linear dumbbell-shaped expression cassettes) in vivo or in vitro. Additionally, nontherapeutic genetic sequences with a negative or positive effect according to the specific application are described, bringing a better comprehension of the technology's state of the art.

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Enhanced cell-mediated IFN-γ-secreting activity against the HIV-1IIIB V3 peptide of the TAB9 multiepitope after DNA vaccine backbone engineering

Cited by 7 publications

References 23 publications

Three types of humanCpG motifs differentially modulate and augment immunogenicity of nonviral and viral repliconDNA vaccines as built‐in adjuvants

Three types of humanCpG motifs differentially modulate and augment immunogenicity of nonviral and viral repliconDNA vaccines as built‐in adjuvants

Prophylactic naked DNA vaccination with the human vascular endothelial growth factor induces an anti-tumor response in C57Bl/6 mice

Nonviral DNA vectors for immunization and therapy: design and methods for their obtention

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