Plasmid encoding papillomavirus Type 16 (HPV16) DNA constructed with codon optimization improved the immunogenicity against HPV infection

Cheung, Y.K.; Cheng, Samuel Chak-Sum; Sin, Fion Wan-Yee; Xie, Yong

doi:10.1016/j.vaccine.2004.07.010

Cited by 51 publications

(34 citation statements)

References 41 publications

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“…Synthetic engineering of the antigen-coding sequences also allowed for the inclusion of other optimization approaches, such as incorporation of a highly efficient leader sequence, improved mRNA stability, and codon optimization in the context of a highly efficient promoter. Together, these enhance transcription and translation, thereby improving expression for greater antigen production (27,28). The antigens were inserted into a modified pVAX1 backbone using the BamHI and XhoI restriction enzyme sites.…”

Section: Design Of Plasmids and In Vitro Antigen Expressionmentioning

confidence: 99%

Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA

et al. 2013

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A vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Plasmodium falciparum malaria; however, a technology for formulating and delivering such a vaccine has remained elusive. Here, we report the preclinical assessment of an optimized DNA vaccine approach that targets four P. falciparum antigens: circumsporozoite protein (CSP), liver stage antigen 1 (LSA1), thrombospondin-related anonymous protein (TRAP), and cell-traversal protein for ookinetes and sporozoites (CelTOS). Synthetic DNA sequences were designed for each antigen with modifications to improve expression and were delivered using in vivo electroporation (EP). Immunogenicity was evaluated in mice and nonhuman primates (NHPs) and assessed by enzyme-linked immunosorbent assay (ELISA), gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay, and flow cytometry. In mice, DNA with EP delivery induced antigen-specific IFN-γ production, as measured by ELISpot assay and IgG seroconversion against all antigens. Sustained production of IFN-γ, interleukin-2, and tumor necrosis factor alpha was elicited in both the CD4(+) and CD8(+) T cell compartments. Furthermore, hepatic CD8(+) lymphocytes produced LSA1-specific IFN-γ. The immune responses conferred to mice by this approach translated to the NHP model, which showed cellular responses by ELISpot assay and intracellular cytokine staining. Notably, antigen-specific CD8(+) granzyme B(+) T cells were observed in NHPs. Collectively, the data demonstrate that delivery of gene sequences by DNA/EP encoding malaria parasite antigens is immunogenic in animal models and can harness both the humoral and cellular arms of the immune system.

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Section: Design Of Plasmids and In Vitro Antigen Expressionmentioning

confidence: 99%

Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA

et al. 2013

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“…Regardless of their potential, an effort has been made to improve their performance through the use of several optimization strategies such as the (1) improvement of the immunological properties of the vector itself through the addition of CpG sequences, capable of acting as an adjuvant [8]; (2) maximization of antigen expression through the use of improved vectors using strong constitutive promoters, addition of regulatory elements that work as transcriptional enhancers, or through codon optimization of the antigen gene sequence [9][10][11]; (3) co-administration of DNA with cytokines and chemokines to amplify the immune response and modulate the Th1 and Th2 profile [12][13][14]; (4) combined administration of DNA with lipid complexes, microparticles or other delivery formulations to increase transfection and expression efficiencies [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Antigen-Targeting Sequences Used in DNA Vaccines

et al. 2009

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Plasmid vectors can be optimized by including specific signals that promote antigen targeting to the major antigen presentation and processing pathways, increasing the immunogenicity and potency of DNA vaccines. A pVAX1-based backbone was used to encode the Green Fluorescence Protein (GFP) reporter gene fused either to ISG (Invariant Surface Glycoprotein) or to TSA (trans-sialidase) Trypanosoma brucei genes. The plasmids were further engineered to carry antigen-targeting sequences, which promote protein transport to the extracellular space (secretion signal), lysosomes (LAMP-1) and to the endoplasmic reticulum (adenovirus e1a). Transfection efficiency was not affected by differences in the size between each construct as no differences in the plasmid copy number per cell were found. This finding also suggests that the addition of both ISG gene and targeting sequences did not add sensitive regions prone to nuclease attack to the plasmid. Cells transfected with pVAX1GFP had a significant higher number of transcripts. This could be a result of lower mRNA stability and/or a lower transcription rate associated with the bigger transcripts. On the other hand, no differences were found between transcript levels of each ISG-GFP plasmids. Therefore, the addition of these targeting sequences does not affect the maturation/stability of the transcripts. Microscopy analysis showed differences in protein localization and fluorescent levels of cells transfected with pVAX1GFP and ISG constructs. Moreover, cells transfected with the lamp and secretory sequences presented a distinct distribution pattern when compared with ISG protein. Protein expression was quantified by flow cytometry. Higher cell fluorescence was observed in cells expressing the cytoplasmic fusion protein (ISG-GFP or TSA-GFP) compared with cells where the protein was transported to the lysosomal pathway. Protein transport to the endoplasmic reticulum does not lead to a decrease in the mean fluorescence values. The secretion signal was only effective when used in conjunction with TSA gene. Therefore, the characteristics of each protein (e.g., presence of transmembrane domains) might influence the efficacy of its cellular transport. This analysis constitutes a useful tool for the optimization of the design of DNA vaccines.

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“…19 The use of recombinant somatotropin has also been investigated. One study showed that the daily injection of somatotropin during early gestation (days [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] selectively improved the growth conditions for low-birth weight littermates. 20 Another study demonstrated that the daily treatment of sows in gestation with porcine somatotropin for 75 days increased offspring size at birth.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone–releasing Hormone Plasmid Treatment by Electroporation Decreases Offspring Mortality Over Three Pregnancies

Person¹,

Bodles-Brakhop²,

Pope³

et al. 2008

Molecular Therapy

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LifeTideSW5 is a growth hormone-releasing hormone (GHRH)-expressing plasmid delivered by intramuscular (IM) electroporation (EP), and the first therapeutic plasmid delivered by this physical method to be approved for use in food animals. Gestating sows (n = 997) were treated once with a single 5-mg GHRH-plasmid by EP or served as controls. Data on offspring from three parities subsequent to treatment were collected. No adverse effects related to treatment were noted. First parity post-treatment offspring from treated sows displayed a 2.93 kg (P < 0.0001) increase in carcass weight (CW), 1.0 mm (P < 0.0001) less back-fat (P2), and a 27.0 g CW/day (P < 0.0001) increase in rate of gain (ROG) compared with controls. An increase of 21.6% was recorded in the number of offspring surviving. In the second and third parities post-treatment, offspring from treated females displayed higher number of born alive and total born number, and lower stillborn rates. Third parity offspring from treated sows displayed a 1.6 kg advantage in CW (P < 0.05), 1.0 mm less P2 (P < 0.05), and a 10.0 g CW/day benefit in ROG. Furthermore, offspring from treated females had a 19.04% lower post-wean loss rate. Overall, plasmid GHRH administration decreased morbidity and mortality in treated females and their offspring over three consecutive pregnancies.

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Plasmid encoding papillomavirus Type 16 (HPV16) DNA constructed with codon optimization improved the immunogenicity against HPV infection

Cited by 51 publications

References 41 publications

Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA

Inducing Humoral and Cellular Responses to Multiple Sporozoite and Liver-Stage Malaria Antigens Using Exogenous Plasmid DNA

Comparative Analysis of Antigen-Targeting Sequences Used in DNA Vaccines

Growth Hormone–releasing Hormone Plasmid Treatment by Electroporation Decreases Offspring Mortality Over Three Pregnancies

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