Toward clinical trials of DNA vaccines against malaria

Hoffman, Stephen L.; Doolan, Denise L.; Wang, Ruobing; Scheller, Libia F.; Kumar, Anita; Weiss, Walter R.; Le, Thong P.; Klinman, Dennis M.; Hobart, Peter; Norman, Jon; Hedstrom, Richard C.

doi:10.1038/icb.1997.59

Cited by 25 publications

(10 citation statements)

References 57 publications

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“…DNA vaccination was shown to be a useful method for inducing specific immune responses (20)(21)(22)(23)(24), and DNA vaccination is in human clinical trials (25)(26)(27)(28)(29). We now report that DNA vaccination with the CD25 gene can protect rats from AA induction.…”

Section: Introductionmentioning

confidence: 82%

DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response

Mimran¹,

Mor²,

Carmi³

et al. 2004

J. Clin. Invest.

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MethodsRats. Female Lewis rats were raised and maintained under pathogen-free conditions in the Animal Breeding Center of the Weizmann Institute. Experiments were carried out under the supervision and guidelines of the Animal Welfare Committee. The rats were 4-6 weeks old at the beginning of the experiments.Plasmids and DNA vaccination. The coding sequence for the α-chain of the rat IL-2 receptor (IL-2Ra; CD25) was cloned into the pcDNA3 expression vector (Invitrogen Corp., San Diego, California, USA) in the BamHI-XbaI sites. The γ-chain of the IL-2 receptor (IL-2Rg) CD132, which is constitutively expressed on T cells (8-10), was cloned in the BamHI-XhoI sites. The empty pcDNA3 vector was used as a control. Plasmid DNA was prepared in large scale using the Qiagen Plasmid Maxi Kit (QIAGEN GmbH, Hilden, Germany). DNA was eluted to a final concentration of 1 mg/ml. In each experiment, groups of eight rats were injected intramuscular-DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response Ab's to the α α-chain of the IL-2 receptor (anti-CD25) are used clinically to achieve immunosuppression. Here we investigated the effects of DNA vaccination with the whole CD25 gene on the induction of rat adjuvant arthritis. The DNA vaccine protected the rats and led to a shift in the cytokine profile of T cells responding to disease target antigens from Th1 to Th2. The mechanism of protection was found to involve the induction of an antiergotypic response, rather than the induction of anti-CD25 Ab's. Antiergotypic T cells respond to activation molecules, ergotopes, expressed on syngeneic activated, but not resting, T cells. CD25-derived peptides function as ergotopes that can be recognized by the antiergotypic T cells. Antiergotypic T cells taken from control sick rats did not proliferate against activated T cells and secreted mainly IFN-γ γ. In contrast, antiergotypic cells from CD25-DNA-protected rats proliferated against activated T cells and secreted mainly IL-10. Protective antiergotypic T cells were found in both the CD4 + and CD8 + populations and expressed α α/ /β β or γ γ/ /δ δ T cell receptors. Antiergotypic α α/ /β β T cells were MHC restricted, while γ γ/ /δ δ T cells were MHC independent. Thus, CD25 DNA vaccination may induce protection from autoimmunity by inducing a cytokine shift in both the antiergotypic response and the response to the antigens targeted in the disease.

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Section: Introductionmentioning

confidence: 82%

DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response

Mimran¹,

Mor²,

Carmi³

et al. 2004

J. Clin. Invest.

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“…The ability of these plasmids to express PyCSP was confirmed in vitro by using an anti-PyCSP mAb (11) and transiently transfected UM449 human melanoma cells (12). All DNA for injection was purified as described (8) by using cesium chloride-ethidium bromide density gradient centrifugation. DNA was solubilized in United States Pharmacopia saline for injection at Ϸ5.0 mg͞ml and was stored at Ϫ20°C.…”

Section: Methodsmentioning

confidence: 99%

“…Protective immunity can be increased, and genetic restriction of the response to each individual protein can be circumvented by immunizing with mixtures of plasmids encoding liver stage proteins (6). Based on our work in mice, we have recently initiated a Phase I clinical trial of a P. falciparum CSP DNA vaccine designed to induce protective CD8ϩ T cells (8).…”

mentioning

confidence: 99%

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine

Sedegah

Jones

Kaur

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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207

150

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“…Finally, DNA is relatively simple to produce and purify in large quantities. Despite these advantages, and the immune responses seen using xenogeneic plasmid DNA immunization in mouse models, DNA vaccines alone have not been sufficient to induce complete or sustained immunity and have had suboptimal potency in humans and nonhuman primates (13,14). Recombinant viral vectors have been investigated as a means of vaccination because they can carry full-length antigen-encoding genes, have the capacity to produce these antigens in large quantities, and may contain helper epitopes.…”

mentioning

confidence: 99%

Comparison of Two Cancer Vaccines Targeting Tyrosinase: Plasmid DNA and Recombinant Alphavirus Replicon Particles

Goldberg

Bartido

Gardner

et al. 2005

Clinical Cancer Research

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Purpose: Immunization of mice with xenogeneic DNA encoding human tyrosinase-related proteins1and 2 breaks tolerance to these self-antigens and leads to tumor rejection.Viral vectors used alone or in heterologous DNA prime/viral boost combinations have shown improved responses to certain infectious diseases. The purpose of this study was to compare viral and plasmid DNA in combination vaccination strategies in the context of a tumor antigen. Experimental Design: Using tyrosinase as a prototypical differentiation antigen, we determined the optimal regimen for immunization with plasmid DNA. Then, using propagation-incompetent alphavirus vectors (virus-like replicon particles, VRP) encoding tyrosinase, we tested different combinations of priming with DNA or VRP followed by boosting with VRP. We subsequently followed antibody production,T-cell response, and tumor rejection.Results: T-cell responses to newly identified mouse tyrosinase epitopes were generated in mice immunized with plasmid DNA encoding human (xenogeneic) tyrosinase. In contrast, when VRP encoding either mouse or human tyrosinase were used as single agents, antibody and T-cell responses and a significant delay in tumor growth in vivo were observed. Similarly, a heterologous vaccine regimen using DNA prime and VRP boost showed a markedly stronger response than DNA vaccination alone. Conclusions: Alphavirus replicon particle vectors encoding the melanoma antigen tyrosinase (self or xenogeneic) induce immune responses and tumor protection when administered either alone or in the heterologous DNA prime/VRP boost approaches that are superior to the use of plasmid DNA alone.

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Toward clinical trials of DNA vaccines against malaria

Cited by 25 publications

References 57 publications

DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response

DNA vaccination with CD25 protects rats from adjuvant arthritis and induces an antiergotypic response

Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine

Comparison of Two Cancer Vaccines Targeting Tyrosinase: Plasmid DNA and Recombinant Alphavirus Replicon Particles

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