I. Poloxamer-Formulated Plasmid DNA-Based Human Cytomegalovirus Vaccine: Evaluation of Plasmid DNA Biodistribution/Persistence and Integration

Vilalta, Adrian; Mahajan, Rohit; Hartikka, Jukka; Rusalov, Denis; Martin, Terrie; Bozoukova, Vesselina; Leamy, Vicky; Hall, Keith B.; Lalor, Peggy; Rolland, Alain; Kaslow, David C.

doi:10.1089/hum.2005.16.ft-116

Cited by 6 publications

(7 citation statements)

References 25 publications

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“…DNA vaccines developed for CMV (265) have focused on the gB, IE1, and pp65 genes as the candidate target immunogens. There are currently phase I clinical trials under way of both a bivalent CMV DNA vaccine candidate, using plasmid DNA encoding pp65 and gB, and a trivalent vaccine candidate, which also includes a third plasmid encoding the IE1 gene product, developed and produced by Vical Vaccines (240,277). The vaccines are formulated using the poloxamer adjuvant CRL1005 and benzalkonium chloride.…”

Section: Vaccinesmentioning

confidence: 99%

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

2009

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SUMMARY Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is considered in the context of the epidemiology of CMV infection in pregnant women and newborn infants, and the clinical manifestations of brain injury are reviewed. The prospects for intervention, including antiviral therapies and vaccines, are summarized. Priorities for future research are suggested to improve the understanding of this common and disabling illness of infancy.

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Section: Vaccinesmentioning

confidence: 99%

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

2009

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“…Microspheres of biodegradable polymers of various chemical compositions have been used to encapsulate DNA vaccines and shown to generate robust immune responses in vivo , presumably due to the sustained supply of antigens and passive targeting of micrometer-size particles to DCs [12]. A number of nano-scale molecular complexes of polymer/DNA vaccine have also been evaluated, using synthetic polycations such as polyethylenimine (PEI) [13] and polylysine [14], naturally derived polycations such as chitosan [15], as well as biodegradable cationic polyesters [16] and block copolymer surfactants [17]. Despite much effort in the past, it remains unclear about the design principles of polymer carrier specific for targeting DNA vaccine to DCs, although it is apparent that one must overcome a multitude of cellular and subcellular barriers generic to gene delivery to any cell type [18], in addition to meeting unique challenges of modulating antigen presentation and the maturation state of DCs.…”

Section: Introductionmentioning

confidence: 99%

Well-defined block copolymers for gene delivery to dendritic cells: Probing the effect of polycation chain-length

Tang

Palumbo

Nagarajan

et al. 2010

Journal of Controlled Release

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The development of safe and efficient polymer carriers for DNA vaccine delivery requires mechanistic understanding of structure-function relationship of the polymer carriers and their interaction with antigen-presenting cells. Here we have synthesized a series of diblock copolymers with well-defined chain-length using atom transfer radical polymerization and characterized the influence of polycation chain-length on the physico-chemical properties of the polymer/DNA complexes as well as the interaction with dendritic cells. The copolymers consist of a hydrophilic poly(ethylene glycol) block and a cationic poly(aminoethyl methacrylate) (PAEM) block. The average degree of polymerization (DP) of the PAEM block was varied among 19, 39, and 75, with nearly uniform distribution. With increasing PAEM chain-length, polyplexes formed by the diblock copolymers and plasmid DNA had smaller average particle size and showed higher stability against electrostatic destabilization by salt and heparin. The polymers were not toxic to mouse dendritic cells (DCs) and only displayed chain-length-dependent toxicity at a high concentration (1 mg/mL). In vitro gene transfection efficiency and polyplex uptake in DCs were also found to correlate with chainlength of the PAEM block with the longer polymer chain favoring transfection and cellular uptake. The polyplexes induced a modest up-regulation of surface markers for DC maturation that was not significantly dependent on PAEM chain-length. Finally, the polyplex prepared from the longest PAEM block (DP of 75) achieved an average of 20% enhancement over non-condensed anionic dextran in terms of uptake by DCs in the draining lymph nodes 24 hours after subcutaneous injection into mice. Insights gained from studying such structurally well-defined polymer carriers and their interaction with dendritic cells may contribute to improved design of practically useful DNA vaccine delivery systems.

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“…The CMV DNA vaccine plasmids contain the same genetic sequence as the targets of many CMV polymerase chain reaction (PCR) assays. The limited data about vaccine kinetics in experimental animals does not provide adequate information for those doing weekly preemptive testing in humans. To facilitate further research, we wanted to study the detectability and pharmacokinetics of the vaccine pDNA in vaccinated patients at our clinical trial site.…”

mentioning

confidence: 99%

Detection and pharmacokinetics of a cytomegalovirus (CMV) DNA plasmid in human plasma during a clinical trial of an intramuscular CMV vaccine in hematopoietic stem cell transplant recipients

Salimnia

Fairfax

Chandrasekar

2014

Transplant Infectious Dis

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Because preemptive treatment of CMV disease in stem cell transplant patients is based on quantitative PCR analysis of viral sequences in plasma, it is important that vaccine sequences not be confused with those in wild-type virus. Confusion could lead to treatment with toxic medications, potentially compromising the transplant. Effects of PCR target choice and amplicon detection techniques on patient management and vaccine trials are discussed.

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I. Poloxamer-Formulated Plasmid DNA-Based Human Cytomegalovirus Vaccine: Evaluation of Plasmid DNA Biodistribution/Persistence and Integration

Cited by 6 publications

References 25 publications

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention

Well-defined block copolymers for gene delivery to dendritic cells: Probing the effect of polycation chain-length

Detection and pharmacokinetics of a cytomegalovirus (CMV) DNA plasmid in human plasma during a clinical trial of an intramuscular CMV vaccine in hematopoietic stem cell transplant recipients

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