Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

Se, Parker; Monteith, David K.; Horton, Holly M.; Hof, R; Hernandez, Pepe; Vilalta, Adrian; Hartikka, Jukka; Hobart, Peter; Bentley, CE; Chang, Alice B.; Hedstrom, Richard C.; Rogers, WO; Kumar, Sanjai; Hoffman, S. L.; Ja, Norman

doi:10.1038/sj.gt.3301491

Cited by 62 publications

(31 citation statements)

References 46 publications

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“…[23][24][25] Many strategies have been used in an attempt to enhance the immunogenicity of DNA vaccines. [26][27][28][29][30][31] It is evident that the potencies of these vaccines depends on amount of the antigen expressed in transfected cells. 6 Therefore, a successful DNA vaccine strategy requires both the efficient delivery of DNA into somatic cells and the appropriate expression of the gene products in the targeted cells.…”

Section: Discussionmentioning

confidence: 99%

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Choi¹,

Jeon²,

Kang³

et al. 2007

Intl Journal of Cancer

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Human sodium iodide symporter (hNIS) is a transmembrane protein that actively transports iodide ions into thyroid cells. hNIS is over-expressed in some cases of the thyroid cancers compared with the surrounding normal tissues and has been considered to be an attractive target for immunotherapy. The aim of this study is to determine the feasibility of utilizing the hNIS antigenic protein in enhanced-antigen-associated immunotherapy using image analysis with a gamma counter. To accomplish this, minimalistic immunogenically defined gene expression (MIDGE), either plain or coupled to a nuclear localization signal (NLS) peptide, was used as a vector system. Vaccination with MIDGE/hNIS, MIDGE/ hNIS-NLS and pcDNA3.1/hNIS produced a significant increase in the number of hNIS-associated IFN-c-secreting CD8 1 T cells, with MIDGE/hNIS having the strongest effect. In addition, immunization with the hNIS encoding vectors induced antigen-mediated antitumor activity against NIS-expressing CT26 tumors in vivo, with the highest tumor free rate (100%) and lowest tumor growth being observed up to 40 days after the CT26/NIS tumor challenge with MIDGE/hNIS than those resulting from other immunization groups. Tumor progression could be followed noninvasively and repetitively by monitoring levels of hNIS gene expression in the tumors using scintigraphic image analysis. Overall, hNIS has a potential use as an antigen for immunization approaches, and vaccination with MIDGE/hNIS vectors is an effective means of generating hNIS-associated immune responses in mice. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Choi¹,

Jeon²,

Kang³

et al. 2007

Intl Journal of Cancer

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“…Plasmid DNA vaccines have been shown to elicit potent humoral and cellular immune responses in a variety of experimental animal models, but the mechanism of immune priming by DNA vaccines remains poorly understood [1][2][3][4][5][6][7]. Following intramuscular injection of a plasmid DNA vaccine, most antigen expression occurs in transfected myocytes at the site of inoculation [1].…”

Section: Introductionmentioning

confidence: 99%

Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4⁺ and CD8⁺ T lymphocyte responses

et al. 2004

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The immunogenicity of plasmid DNA vaccines may be limited by the availability of professional antigen-presenting cells (APC) at the site of inoculation. Here we demonstrate that the types of APC recruited to the injection site can selectively modulate CD4 + or CD8 + T lymphocyte responses elicited by an HIV-1 Env DNA vaccine in mice. Coadministration of plasmid GM-CSF with the DNA vaccine resulted in the recruitment of macrophages to the site of inoculation and specifically augmented vaccine-elicited CD4 + T lymphocyte responses. In contrast, coadministration of plasmid MIP-1 § with the DNA vaccine resulted in the recruitment of dendritic cells to the injection site and enhanced vaccine-elicited CD8 + T lymphocyte responses. Interestingly, coadministration of both plasmid GM-CSF and plasmid MIP-1 § with the DNA vaccine recruited both macrophages and dendritic cells and led to a synergistic and sustained augmentation of CD4 + and CD8 + T lymphocyte responses. These data demonstrate the critical importance of locally recruited professional APC in determining the magnitude and nature of immune responses elicited by plasmid DNA vaccines. Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses.

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“…Our laboratories and others have demonstrated that the addition of plasmids expressing cytokines and immunomodulatory molecules can substantially augment DNA vaccine-elicited immune responses in both mice and nonhuman primates (3,4,15,16,21,34,37). However, the practical requirements of manufacturing and establishing the safety of the plasmid cytokines prior to the initiation of clinical trials may prove a limitation of this strategy (7,26). Other approaches involve the addition of polymer adjuvants (29) and the use of in vivo electroporation techniques (24,35).…”

mentioning

confidence: 99%

A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates

Barouch

Yang

Kong

et al. 2005

J Virol

156

139

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Plasmid DNA vaccines elicit potent and protective immune responses in numerous small-animal models of infectious diseases. However, their immunogenicity in primates appears less potent. Here we investigate a novel approach that optimizes regulatory elements in the plasmid backbone to improve the immunogenicity of DNA vaccines. Among various regions analyzed, we found that the addition of a regulatory sequence from the R region of the long terminal repeat from human T-cell leukemia virus type 1 (HTLV-1) to the cytomegalovirus (CMV) enhancer/promoter increased transgene expression 5-to 10-fold and improved cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens. In cynomolgus monkeys, DNA vaccines containing the CMV enhancer/promoter with the HTLV-1 R region (CMV/R) induced markedly higher cellular immune responses to HIV-1 Env from clades A, B, and C and to HIV-1 Gag-Pol-Nef compared with the parental DNA vaccines. These data demonstrate that optimization of specific regulatory elements can substantially improve the immunogenicity of DNA vaccines encoding multiple antigens in small animals and in nonhuman primates. This strategy could therefore be explored as a potential method to enhance DNA vaccine immunogenicity in humans.Plasmid DNA vaccines have shown promise as a novel vaccination modality based on their simplicity and versatility (31,32,36). In particular, DNA vaccines can elicit potent and protective cellular and humoral immune responses in a variety of small-animal models (10). However, they have proven substantially less immunogenic in nonhuman primate studies and in clinical trials to date (8,19,33).Several approaches have been explored to improve the immunogenicity of DNA vaccines. Our laboratories and others have demonstrated that the addition of plasmids expressing cytokines and immunomodulatory molecules can substantially augment DNA vaccine-elicited immune responses in both mice and nonhuman primates (3,4,15,16,21,34,37). However, the practical requirements of manufacturing and establishing the safety of the plasmid cytokines prior to the initiation of clinical trials may prove a limitation of this strategy (7, 26). Other approaches involve the addition of polymer adjuvants (29) and the use of in vivo electroporation techniques (24, 35). These strategies have similarly proven effective in animal models, but their practical utility in clinical trials has yet to be demonstrated.In this study, we investigate a novel strategy involving optimization of regulatory elements in the backbone of the plasmid DNA vaccine. DNA vaccines often utilize a cytomegalovirus (CMV) enhancer, promoter, and intron to drive high-level expression of a transgene in mammalian cells (32,38). Here, we explore the effects of adding the regulatory R region from the 5Ј long terminal repeat (LTR) of human T-cell leukemia virus type 1 (HTLV-1), which acts as a transcriptional and posttranscriptional enhancer (30). We find that these CMV/R DNA vaccines elicit substantially higher human immunodeficiency viru...

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Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

Cited by 62 publications

References 46 publications

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4⁺ and CD8⁺ T lymphocyte responses

A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates

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Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine

Cited by 62 publications

References 46 publications

MIDGE/hNIS vaccination generates antigen‐associated CD8+IFN‐γ+ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8+IFN‐γ+ T cells and enhances protective antitumor immunity

Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4+ and CD8+ T lymphocyte responses

A Human T-Cell Leukemia Virus Type 1 Regulatory Element Enhances the Immunogenicity of Human Immunodeficiency Virus Type 1 DNA Vaccines in Mice and Nonhuman Primates

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MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

MIDGE/hNIS vaccination generates antigen‐associated CD8⁺IFN‐γ⁺ T cells and enhances protective antitumor immunity

Recruitment of different subsets of antigen‐presenting cells selectively modulates DNA vaccine‐elicited CD4⁺ and CD8⁺ T lymphocyte responses