Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques

Luckay, Amara; Sidhu, Maninder K.; Kjeken, Rune; Megati, Shakuntala; Chong, Siew-Yen; Roopchand, Vidia; Garcia-Hand, Dorys; Abdullah, Rashed; Braun, Ralph; Montefiori, David C.; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Mathiesen, Iacob; Israel, Zimra R.; Eldridge, John H.; Egan, Michael A.

doi:10.1128/jvi.00055-07

Cited by 183 publications

(121 citation statements)

References 81 publications

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“…In addition, electroporation induced a broader repertoire of cellular immune responses against subdominant antigens including preS, Core, and Pol, even though the magnitude was not as great as with the S antigen. These encouraging data are consistent with previous reports regarding the potency of EP-based plasmid DNA vaccination in large animals, including monkeys (Luxembourge et al, 2005;Otten et al, 2006;Luckay et al, 2007).…”

Section: Discussionsupporting

confidence: 82%

“…It has been reported that the magnitude of immune responses induced in primates is lower than that in small animals, and the quantity of DNA required for the effective immunization of primates is significantly higher (mg vs μg) (Aihara et al, 1998;Selby et al, 2000). Electroporation (EP) resolves this problem via the introduction of plasmid DNA into the cells to a degree adequate for optimal immune response at low dosages (Luckay et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

et al. 2008

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Pulse-induced permeabilization of cellular membranes, generally referred to as electroporation (EP), has been used for years as a tool to increase macromolecule uptake in tissues, including nucleic acids, for gene therapeutic applications, and this technique has been shown to result in improved immunogenicity. In this study, we assessed the utility of EP as a tool to improve the efficacy of HB-110, a novel therapeutic DNA vaccine against chronic hepatitis B, now in phase 1 of clinical study in South Korea. The potency of HB-110 in mice was shown to be improved by EP. The rapid onset of antigen expression and higher magnitude of humoral and cellular responses in electric pulse-treated mice revealed that EP may enable a substantial reduction in the dosage of DNA vaccine required to elicit a response similar in magnitude to that achievable via conventional administration. This study also showed that EP-based vaccination at 4-week-intervals elicited a cellular immune response which was about two-fold higher than the response elicited by conventional vaccination at 2-week intervals. These results may provide a rationale to reduce the clinical dose and increase the interval between the doses in the multidose vaccination schedule. Electric pulsing also elicited a more balanced immune response against four antigens expressed by HB-110: S, preS, Core, and Pol.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

et al. 2008

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“…3 Extensive investigation by many groups over the past decade has enabled vast improvements in the technology and transduction efficiency, 2 such that it has now been successfully used in pre-clinical and clinical trials for the delivery of therapeutic plasmids 4 and DNA vaccines. 5,6 However, two unresolved aspects of ET are the underlying nature of any tissue response to the ET process as a measure of safety and/or any immunological response induced by the procedure and/or nucleic acid itself. With regard to safety, the continued evolution of new ET conditions and non-viral delivery agents towards the clinic necessitates a firm understanding of tissue responses and the development of appropriate tools for assessing and minimising potential adverse events.…”

Section: Introductionmentioning

confidence: 99%

Molecular signature of the immune and tissue response to non-coding plasmid DNA in skeletal muscle after electrotransfer

et al. 2011

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Electrotransfer of plasmid DNA in skeletal muscle is a common non-viral delivery method for both therapeutic genes and DNA vaccines. Yet, despite the similar approaches, an immune response is detrimental in gene therapy, but desirable for vaccines. However, the full nature of the immune and tissue responses to nucleic acids and electrotransfer in skeletal muscle has not been addressed. Here we used microarray analysis, fluorescence-activated cell sorting and quantitative polymerase chain reaction to obtain the molecular and cellular signature of the tissue and immune response to electrotransfer of saline and non-coding plasmid DNA. Saline electrotransfer resulted in limited infiltration and induction of a moderate damage --repair gene expression pattern not involving innate immune activation. However, plasmid electrotransfer augmented expression of the same genes in addition to inducing a strong innate immune response associated with pro-inflammatory infiltration. In particular, the inflammasome, Toll-like receptor 9 and other pattern recognition receptors able to respond to cytoplasmic DNA were upregulated. Several key differences in the nature of the inflammatory infiltrate and the kinetics of gene expression were also identified when comparing electrotransfer of conventional and CpG-free plasmids. Our data provide insights into the mechanisms of DNA detection and response in muscle that has relevance for non-viral gene therapy and DNA vaccination.

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“…Among the most striking advances for plasmid delivery in vivo the most potent has been that of electroporation (EP). Studies have showed that EP has been a feasible method for DNA vaccine delivery to enhance both cellular and humoral responses (23,24).…”

mentioning

confidence: 99%

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

Yan

Harris

Khan³

et al. 2008

Vaccine

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Human papilloma-virus (HPV) infection is the major cause of cervical cancer. HPV 18 is the most prevalence high-risk HPV after type 16 that accounts for the largest number of cervical cancer cases worldwide. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines for targeting tumors post infection. In this study, we utilize a novel multi-phase strategy for HPV 18 antigen development with the goal of increasing anti-HPV18 cellular immunity. Our data show that this construct can induce strong cellular immune responses against HPV 18 E6 and E7 antigens in a murine model. Moreover, when applied to Rhesus monkeys, this construct is also able to elicit cellular immunity. These data suggest such DNA immunogens are candidates for further study in the eventual context of immunotherapy for HPV-associated cancers.

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Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques

Abstract: Since human immunodeficiency virus (HIV)-

Cited by 183 publications

References 81 publications

Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

Increased in vivo immunological potency of HB-110, a novel therapeutic HBV DNA vaccine, by electroporation

Molecular signature of the immune and tissue response to non-coding plasmid DNA in skeletal muscle after electrotransfer

Cellular immunity induced by a novel HPV18 DNA vaccine encoding an E6/E7 fusion consensus protein in mice and rhesus macaques

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