Antigen design enhances the immunogenicity of Semliki Forest virus-based therapeutic human papillomavirus vaccines.

Abstract:

:Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the relatively low intrinsic immunogenicity of DNA vaccines could be enhanced by inclusion of endoplasmic reticulum (ER) targeting and universal helper epitopes within the vaccine. We now evaluated whether an optimal antigen format, as defined in DNA vaccines, can further enhance the effectiveness of recombinant Semliki Forest virus (rSFV) vaccines. To this purpose, we generated, characterized and evaluated the efficacy of rSFV replicon particles expressing human papillomavirus E6 and/or E7 proteins fused to several helper T-cell epitopes and an ER targeting signal. Here, we show that inclusion of a helper cassette and an ER targeting signal enhanced protein stability and markedly augmented the frequencies of human papillomavirus-specific T cells. Even at an immunization dose of as low as 10(5) replicon particles, this novel vaccine achieved tumor regression and protection. Thus, even highly effective viral vector vaccines can benefit from an improved antigen format, based on the inclusion of defined helper epitopes and ER targeting.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Ip PP,Boerma A,Walczak M,Oosterhuis K,Haanen JB,Schumacher TN,Nijman HW,Daemen T

doi

10.1038/gt.2015.24

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

560-7

issue

7

eissn

0969-7128

issn

1476-5462

pii

gt201524

journal_volume

22

pub_type

杂志文章
  • Human mesenchymal stem cells: from basic biology to clinical applications.

    abstract::Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3303067

    authors: Abdallah BM,Kassem M

    更新日期:2008-01-01 00:00:00

  • An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model.

    abstract::Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302349

    authors: Hashimoto M,Rockenstein E,Mante M,Crews L,Bar-On P,Gage FH,Marr R,Masliah E

    更新日期:2004-12-01 00:00:00

  • Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats.

    abstract::Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.183

    authors: Ogura M,Urabe M,Akimoto T,Onishi A,Ito C,Ito T,Tsukahara T,Mizukami H,Kume A,Muto S,Kusano E,Ozawa K

    更新日期:2012-05-01 00:00:00

  • Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA.

    abstract::Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302786

    authors: Konstantinova P,de Vries W,Haasnoot J,ter Brake O,de Haan P,Berkhout B

    更新日期:2006-10-01 00:00:00

  • Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus).

    abstract::Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.87

    authors: Alba R,Bradshaw AC,Mestre-Francés N,Verdier JM,Henaff D,Baker AH

    更新日期:2012-01-01 00:00:00

  • Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector.

    abstract::One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor f...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300974

    authors: Nathwani AC,Persons DA,Stevenson SC,Frare P,McClelland A,Nienhuis AW,Vanin EF

    更新日期:1999-08-01 00:00:00

  • Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss.

    abstract::Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this st...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.139

    authors: Yu H,Li Q,Herbert B,Zinna R,Martin K,Junior CR,Kirkwood KL

    更新日期:2011-04-01 00:00:00

  • RNA interference in embryonic stem cells and the prospects for future therapies.

    abstract::In 1998, two distinct and exciting scientific fields emerged which have profoundly shaped the current direction of biomedical research. The discovery of RNA interference (RNAi) and the derivation of human embryonic stem (ES) cells have yielded exciting new possibilities for researchers and clinicians alike. While fund...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302723

    authors: Heidersbach A,Gaspar-Maia A,McManus MT,Ramalho-Santos M

    更新日期:2006-03-01 00:00:00

  • Gene therapy progress and prospects: RNA aptamers.

    abstract::Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody- and small-molecule-based thera...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302900

    authors: Que-Gewirth NS,Sullenger BA

    更新日期:2007-02-01 00:00:00

  • Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

    abstract::We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate marke...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300565

    authors: Morsy MA,Gu MC,Zhao JZ,Holder DJ,Rogers IT,Pouch WJ,Motzel SL,Klein HJ,Gupta SK,Liang X,Tota MR,Rosenblum CI,Caskey CT

    更新日期:1998-01-01 00:00:00

  • Electropermeabilization of skeletal muscle enhances gene transfer in vivo.

    abstract::This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300847

    authors: Mathiesen I

    更新日期:1999-04-01 00:00:00

  • Regeneration of pancreatic islets in vivo by ultrasound-targeted gene therapy.

    abstract::This study uses a novel approach to gene therapy in which plasmid DNA is targeted to the pancreas in vivo using ultrasound-targeted microbubble destruction (UTMD) to achieve islet regeneration. Intravenous microbubbles carrying plasmids are destroyed within the pancreatic microcirculation by ultrasound, achieving loca...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.85

    authors: Chen S,Shimoda M,Wang MY,Ding J,Noguchi H,Matsumoto S,Grayburn PA

    更新日期:2010-11-01 00:00:00

  • Particle-mediated gene transfer into murine livers using a newly developed gene gun.

    abstract::Although particle-mediated gene transfer using gene gun technology has been applied for gene transfer into epidermis, applications of this technology to visceral tissues have not been well investigated. Although all helium gas-driven gene gun instruments have used macrocarriers to discharge DNA-coated microprojectiles...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301192

    authors: Kuriyama S,Mitoro A,Tsujinoue H,Nakatani T,Yoshiji H,Tsujimoto T,Yamazaki M,Fukui H

    更新日期:2000-07-01 00:00:00

  • APOBEC3A catabolism of electroporated plasmid DNA in mouse muscle.

    abstract::The mouse is widely used as a model for DNA therapy and vaccination even though the efficiency of DNA delivery in higher mammals and humans is much less. The human APOBEC3 (A3) enzymes impact viral genomes by cytidine deamination, which introduces multiple uridine residues into single-stranded DNA, a process known as ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.88

    authors: Kostrzak A,Henry M,Demoyen PL,Wain-Hobson S,Vartanian JP

    更新日期:2015-01-01 00:00:00

  • Functional and phenotypic variations in human T cells subjected to retroviral-mediated gene transfer.

    abstract::The insertion of suicide genes in donor T lymphocytes constitutes the basis of new approaches aiming at the treatment of the graft-versus-host disease (GVHD), a frequent complication in recipients of allogeneic haematopoietic grafts. In this study we investigated the impact that the ex vivo manipulation required for t...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302188

    authors: Lamana ML,Bueren JA,Vicario JL,Balas A

    更新日期:2004-03-01 00:00:00

  • Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    abstract::Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we te...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.121

    authors: Hordeaux J,Dubreil L,Deniaud J,Iacobelli F,Moreau S,Ledevin M,Le Guiner C,Blouin V,Le Duff J,Mendes-Madeira A,Rolling F,Cherel Y,Moullier P,Colle MA

    更新日期:2015-04-01 00:00:00

  • Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.

    abstract::The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted i...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300671

    authors: Löhr M,Müller P,Karle P,Stange J,Mitzner S,Jesnowski R,Nizze H,Nebe B,Liebe S,Salmons B,Günzburg WH

    更新日期:1998-08-01 00:00:00

  • Efficient in vivo transduction of the neonatal mouse liver with pseudotyped retroviral vectors.

    abstract::Ideal methods for human gene therapy will eventually include direct gene transfer to defective tissues in a patient in vivo. Toward that goal, we have used high titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Miyanohara A,Yee JK,Bouic K,LaPorte P,Friedmann T

    更新日期:1995-03-01 00:00:00

  • Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap.

    abstract::Retroviral vectors have become the primary tool for gene delivery into hematopoietic cells, including T lymphocytes. Lentiviral vectors offer an advantage over Moloney murine leukemia virus (MuLV) vectors because of their ability to translocate across an intact nuclear membrane and integrate into the genome of nonprol...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301378

    authors: Dardalhon V,Herpers B,Noraz N,Pflumio F,Guetard D,Leveau C,Dubart-Kupperschmitt A,Charneau P,Taylor N

    更新日期:2001-02-01 00:00:00

  • Adeno-associated virus vector enables safe and efficient Cas9 activation in neonatal and adult Cas9 knockin murine cochleae.

    abstract::Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-020-0124-1

    authors: Kang W,Zhao X,Sun Z,Dong T,Jin C,Tong L,Zhu W,Tao Y,Wu H

    更新日期:2020-08-01 00:00:00

  • HSV vector-mediated transduction and GDNF secretion from adipose cells.

    abstract::The accessibility of adipose tissue and its ability to secrete various bioactive molecules suggest that adipose cells may be attractive targets for gene therapy applications. Here, we report the use of highly defective herpes simplex virus (HSV) vectors as suitable gene transfer agents for adipose cells in culture and...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302359

    authors: Fradette J,Wolfe D,Goins WF,Huang S,Flanigan RM,Glorioso JC

    更新日期:2005-01-01 00:00:00

  • MuLV-based vectors pseudotyped with truncated HIV glycoproteins mediate specific gene transfer in CD4+ peripheral blood lymphocytes.

    abstract::Human immunodeficiency virus (HIV) infection ultimately leads to the destruction of the CD4+ lymphocyte subset and the onset of AIDS. In recent years, several gene therapy procedures making use of retroviral vectors that selectively target HIV susceptible cells have been proposed in order to interfere with HIV product...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300646

    authors: Lodge R,Subbramanian RA,Forget J,Lemay G,Cohen EA

    更新日期:1998-05-01 00:00:00

  • Correction of argininosuccinate synthetase (AS) deficiency in a murine model of citrullinemia with recombinant adenovirus carrying human AS cDNA.

    abstract::Citrullinemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthetase (AS). It is characterized by elevated levels of blood citrulline and ammonia, which often results in hyperammonemic coma and early neonatal death in affected children. We have explored the use of adenoviral vector...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301303

    authors: Ye X,Whiteman B,Jerebtsova M,Batshaw ML

    更新日期:2000-10-01 00:00:00

  • Rapid identification of viable retrovirus-transduced cells using the green fluorescent protein as a marker.

    abstract::Various methods for determining the expression of the beta-galactosidase (beta-gal) gene after retroviral transduction were compared as a means to assess retroviral titre. To allow better comparison, different retroviral vectors were constructed carrying two mutants of the green fluorescent protein and assessed as sen...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300519

    authors: Klein D,Indraccolo S,von Rombs K,Amadori A,Salmons B,Günzburg WH

    更新日期:1997-11-01 00:00:00

  • T-cell response to adenovirus hexon and DNA-binding protein in mice.

    abstract::The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302232

    authors: McKelvey T,Tang A,Bett AJ,Casimiro DR,Chastain M

    更新日期:2004-05-01 00:00:00

  • Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options.

    abstract::Studies reviewed show that lentiviral gene therapy directed either at inhibiting the synthesis of brain acetaldehyde generated from ethanol or at degrading brain acetaldehyde fully prevent ethanol intake by rats bred for their high alcohol preference. However, after animals have chronically consumed alcohol, the above...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/s41434-019-0064-9

    authors: Yedy Israel,Quintanilla ME,Ezquer F,Morales P,Rivera-Meza M,Karahanian E,Ezquer M,Herrera-Marschitz M

    更新日期:2019-11-01 00:00:00

  • Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury.

    abstract::The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302516

    authors: da Cruz MT,Cardoso AL,de Almeida LP,Simões S,de Lima MC

    更新日期:2005-08-01 00:00:00

  • Induction of stable RNA interference in mammalian cells.

    abstract::Over the last years, RNA interference (RNAi) has become a widely used technique that permits the knock-down, and hence functional analysis, of individual genes in vertebrate cells. However, the high failure rate of the RNA molecules used in RNAi experiments continues to be a problem. In this paper, I describe a set of...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302656

    authors: Cullen BR

    更新日期:2006-03-01 00:00:00

  • Widespread transduction of astrocytes and neurons in the mouse central nervous system after systemic delivery of a self-complementary AAV-PHP.B vector.

    abstract::Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype most effective in crossing the blood-brain barrier (BBB) and transducing cells of the central nervous system (CNS), following systemic injection. However, a newly engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher ef...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-018-0005-z

    authors: Rincon MY,de Vin F,Duqué SI,Fripont S,Castaldo SA,Bouhuijzen-Wenger J,Holt MG

    更新日期:2018-04-01 00:00:00

  • Low-speed centrifugation of retroviral vectors absorbed to a particulate substrate: a highly effective means of enhancing retroviral titre.

    abstract::For many gene therapy applications the effective titre of retroviral vectors is a limiting factor both in vitro and in vivo. Purification and concentration of retrovirus from packaging cell supernatant can overcome this problem. To this end we have investigated a novel procedure which involves complexing retrovirus to...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301201

    authors: Darling D,Hughes C,Galea-Lauri J,Gäken J,Trayner ID,Kuiper M,Farzaneh F

    更新日期:2000-06-01 00:00:00