<i>In Vivo</i>Electroporation of Minicircle DNA as a Novel Method of Vaccine Delivery To Enhance HIV-1-Specific Immune Responses

Wang, Qingtao; Jiang, Wei; Chen, Yongqin David; Liu, Pengyu; Sheng, Chunjie; Chen, Shuai; Zhang, Hui; Pan, Ci; Gao, Shan; Huang, Wenlin

doi:10.1128/jvi.02757-13

Cited by 39 publications

(27 citation statements)

References 63 publications

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“…These data are consistent with previous reports using DNA minicircles. 25,26 For example, Dietz and others have shown that a minicircle expressing ovalbumin produced greater SIINFEKL tetramer C CD8 C T cells and protected against infection in a modified listeriosis model. 26 Previous reports, however, have not examined regulatory marker expression or complete Th1 cytokine expression profiles of minicircle-elicited CD8 C T cell responses, both of which have been shown to be important for antitumor efficacy.…”

Section: Cd8mentioning

confidence: 99%

“…[22][23][24] Recently, DNA minicircles were reported to elicit greater frequencies of antigen-specific CD8 C T cells when compared to conventional plasmid immunization, and minicircle immunization was able to better protect against infection by an intracellular bacterium. 25,26 However, these studies did not evaluate the efficacy of minicircle DNA immunization as an antitumor therapy. Further, to our knowledge, there have been no reports exploring the efficacy of MIP vaccination in any setting.…”

Section: Introductionmentioning

confidence: 99%

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Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses

2016

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Increasing transgene expression has been a major focus of attempts to improve DNA vaccine-induced immunity in both preclinical studies and clinical trials. Novel mini-intronic plasmids (MIPs) have been shown to cause elevated and sustained transgene expression in vivo. We sought to test the antitumor activity of a MIP, compared to standard DNA plasmid immunization, using the tumor-specific antigen SSX2 in an HLA-A2-restricted tumor model. We found that MIP vaccination elicited a greater frequency of antigen-specific CD8C T cells when compared to conventional plasmid, and protected animals from subsequent tumor challenge. However, therapeutic vaccination with the MIP resulted in an inferior antitumor effect, and CD8C tumor-infiltrating lymphocytes from these mice expressed higher levels of surface LAG3. Antitumor efficacy of MIP vaccination could be recovered upon antibody blockade of LAG3. In non-tumor bearing mice, MIP immunization led to a loss of epitope dominance, attenuated CD8 C cytokine responses to the dominant p103 epitope, and increased LAG3 expression on p103-specific CD8 C T cells. Further, LAG3 expression on CD8 C T cells was associated with antigen dose and persistence in spite of DNA-induced innate immunity. These data suggest that for antitumor immunization, approaches leading to increased antigen expression following vaccination might optimally be combined with LAG3 inhibition in human trials. On the other hand, mini-intronic vector approaches may be a superior means to elicit LAG3-dependent tolerance in the treatment of autoimmune diseases.

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Section: Cd8mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses

2016

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“…A recent approach to overcome this is the use of electroporation, thus increasing passage of the vaccine into the cell, at the same time increasing APC recruitment to the site of vaccination [30]. Currently, no DNA vaccines with electroporation against intracellular pathogens have reached clinical trials, however the approach has been employed in both HIV and influenza vaccines in mice, with results showing increased immunogenicity following electroporation [31,32]. …”

Section: Vectored Vaccinesmentioning

confidence: 99%

Novel vaccine approaches for protection against intracellular pathogens

Griffiths¹,

Khader²

2014

Current Opinion in Immunology

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Vaccination against intracellular pathogens requires generation of a pool of memory T cells able to respond upon infection and mediate either killing of the infected cell or induce killing mechanisms in the infected cell. T cell-inducing vaccines must aim to target the antigen to antigen-presenting cells so that it can be presented on MHC molecules on the cell surface. Methods to do this include making use of vectors such as plasmid DNA or viruses, live attenuated pathogens or subunit vaccines targeted and enhanced using adjuvants. The choice of approach should be guided by the phenotype and localization of the desired T cell response. This review will discuss current approaches in the pipeline for the development of T cell-inducing vaccines, including vectored, live attenuated, and subunit vaccines.

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“…This report further described greater protection upon challenge with a Listeria monocytogenes strain expressing ovalbumin using prophylactic minicircle immunization. Similarly, Wang et al demonstrated that electroporation of a minicircle encoding a codon-optimized HIV1 gag gene elicited greater frequencies of IFNγ-secreting CD8+ T cells (Wang et al, 2013). These data would suggest that use of minicircle or mini-intronic plasmids should similarly yield greater cell mediated immunity and resultant anti-tumor benefit in tumor models.…”

Section: Dna Vaccines – Mechanisms Of Action; Increasing Immunogenmentioning

confidence: 99%

DNA vaccines for prostate cancer

Zahm

Colluru

McNeel

2017

Pharmacology & Therapeutics

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DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines. In addition, studies into the mechanisms of tumor resistance to anti-tumor vaccination have suggested combination approaches that can increase the antitumor effect of DNA vaccines. This review focuses on these mechanisms of action and mechanisms of resistance using DNA vaccines, and how this information is being used to improve the anti-tumor effect of DNA vaccines. These approaches are then specifically discussed in the context of human prostate cancer, a disease for which DNA vaccines have been and continue to be explored as treatments.

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In VivoElectroporation of Minicircle DNA as a Novel Method of Vaccine Delivery To Enhance HIV-1-Specific Immune Responses

Cited by 39 publications

References 63 publications

Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses

Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses

Novel vaccine approaches for protection against intracellular pathogens

DNA vaccines for prostate cancer

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In VivoElectroporation of Minicircle DNA as a Novel Method of Vaccine Delivery To Enhance HIV-1-Specific Immune Responses

Cited by 39 publications

References 63 publications

Mini-intronic plasmid vaccination elicits tolerant LAG3+CD8+T cells and inferior antitumor responses

Mini-intronic plasmid vaccination elicits tolerant LAG3+CD8+T cells and inferior antitumor responses

Novel vaccine approaches for protection against intracellular pathogens

DNA vaccines for prostate cancer

Contact Info

Product

Resources

About

Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses

Mini-intronic plasmid vaccination elicits tolerant LAG3⁺CD8⁺T cells and inferior antitumor responses