Abstract:
:La Crosse virus (LACV)-mediated encephalitis is the most frequently reported arboviral disease in the United States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an age-independent susceptibility to LACV and develop an acute encephalitis within 6 days of infection, thereby allowing the evaluation of vaccines against LACV. Taking advantage of this knockout mouse model, we have assessed the feasibility of DNA vaccination against this viral disease. Plasmid DNAs, encoding either the virus surface glycoproteins G1 and G2 or the internal nucleocapsid protein N, were used to immunize IFNAR-1-deficient mice. Mice vaccinated with DNA encoding the glycoproteins G1 and G2 produced neutralizing antibodies and exhibited a high degree of protection against challenge with high doses of LACV. Depletion of CD4+ T cells in mice vaccinated with DNA encoding G1/G2 reduced their capacity to control the infection. Virus titration and immunohistological analysis revealed that the protected mice showed no evidence of LACV particles in the brain. This indicates that the vaccine-induced immune response efficiently blocked viral spreading from the primary replication site to the brain. In contrast, immunization with DNA encoding protein N yielded only a partial protective effect that can be attributed to the cellular immune response. Taken together, this study shows that DNA vaccines can be designed to efficiently induce a protective immune response based on neutralizing antibodies and CD4+ T cells.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Schuh T,Schultz J,Moelling K,Pavlovic Jdoi
10.1089/10430349950017653keywords:
subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1649-58issue
10eissn
1043-0342issn
1557-7422journal_volume
10pub_type
杂志文章abstract::Transferring therapeutic genes into the nociceptive system, including dorsal root ganglia (DRGs) and the spinal cord, is potentially a powerful approach for the treatment of chronic pain in humans. Adeno-associated viral vectors (AAVs) are particularly useful in delivering foreign genes to targeted tissues because the...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403765701187
更新日期:2003-06-10 00:00:00
abstract::Expression of a gene encoding the diphtheria toxin A (DT-A) fragment, controlled by tissue specific regulatory elements, has previously been used to kill selected cell populations. Here, we have examined the feasibility of controlling DT-A expression using regulatory systems from the human immunodeficiency virus (HIV-...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1991.2.1-53
更新日期:1991-04-01 00:00:00
abstract::Clinical trials of gene therapy using a viral delivery system for glioma have been limited. Recently, gene therapy using stem cells as the vehicles for delivery of therapeutic agents has emerged as a new treatment strategy for malignant brain tumors. In this study, we used human umbilical cord blood-derived mesenchyma...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.187
更新日期:2011-06-01 00:00:00
abstract::Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.150
更新日期:2019-06-01 00:00:00
abstract::This study focuses on the design, construction, and evaluation of a chimeric promoter for gene therapy applications where it is desirable to have low-level basal expression of the newly transferred gene, which can be induced to higher levels of expression by the administration of pharmacologic agents that can be safel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.15-1883
更新日期:1996-10-01 00:00:00
abstract::Adenoviruses (Ads) have shown great utility as vectors for the delivery of genes to mammalian cells, partly because of their ability to infect a wide range of different cell types independent of the replicative state of the cell. However, Ads do not transduce mature muscle efficiently because of low levels of the natu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303404772679986
更新日期:2004-02-01 00:00:00
abstract::Targeted integration into a genomic safe harbor, such as the AAVS1 locus on chromosome 19, promises predictable transgene expression and reduces the risk of insertional mutagenesis in the host genome. The application of gamma-retroviral long terminal repeat (LTR)-driven vectors, which semirandomly integrate into the g...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.194
更新日期:2020-02-01 00:00:00
abstract::Glycogen storage disease type II (GSDII) is a lysosomal storage disease caused by a deficiency in acid alpha-glucosidase (GAA), and leads to cardiorespiratory failure by the age of 2 years. In this study, we investigate the impact of anti-GAA antibody formation on cross-correction of the heart, diaphragm, and hind-lim...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.68
更新日期:2005-01-01 00:00:00
abstract::Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector pack...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.5-635
更新日期:1995-05-01 00:00:00
abstract::Adeno-associated viral (AAV) vectors containing cone-specific promoters have rescued cone photoreceptor function in mouse and dog models of achromatopsia, but cone-specific promoters have not been optimized for use in primates. Using AAV vectors administered by subretinal injection, we evaluated a series of promoters ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.130
更新日期:2016-01-01 00:00:00
abstract::When transferring the human multidrug resistance 1 (MDR1) cDNA, FMEV retroviral vectors mediate high-dose multidrug resistance and, thus, background-free selection in primary human hematopoietic progenitor cells. Here, we analyzed strategies for co-expression of a second gene from an FMEV:MDR1 vector. When linking the...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.1-33
更新日期:1998-01-01 00:00:00
abstract::Adenovirus vectors transduce liver hepatocytes with extreme efficiency; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs) in the liver in a process that resembles a number of human diseases, including viral ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950019048
更新日期:1999-01-20 00:00:00
abstract::Gene therapy studies in primates can provide important information regarding vector tropism, specific cellular expression, biodistribution, and safety prior to clinical trials. In this study, we report the assessment of transduction efficiency of recombinant adeno-associated virus (rAAV) vectors using human postmortem...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.157
更新日期:2011-05-01 00:00:00
abstract::As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurolo...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.7-1093
更新日期:1998-05-01 00:00:00
abstract::The T cell co-stimulatory molecule B7-1 was transduced into a poorly immunogenic murine neuroblastoma cell line (Neuro-2a, N-2a) alone or in combination with MHC class II genes to test the ability of these genes to stimulate antitumor immunity. N-2a cells transduced with B7-1 exhibited reduced tumorigenicity, whereas ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.17-2059
更新日期:1996-11-10 00:00:00
abstract::Based on the K8/JTS-1-mediated transfection technique, we developed an in vivo protocol for an efficient transfer of plasmid DNA to ocular cells. As determined with condensed plasmids containing reporter genes for either beta-galactosidase (pcDNA-lacZ) or enhanced green fluorescent protein (pREP-EGFP), the immortalize...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050129495
更新日期:2000-09-01 00:00:00
abstract::The gene therapy strategy using the hsvl-thymidine kinase gene (TK) and ganciclovir (GCV) injections that has been used for treating human glioblastomas has not been as effective as expected after the first animal experiments. A better understanding of the different steps involved in this treatment, like gene transfer...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.16-1945
更新日期:1997-11-01 00:00:00
abstract::The rapid inactivation of murine-derived retroviral vectors in human or nonhuman primate sera is largely attributed to the activity of complement mediated through the classical pathway. In this study, we have further investigated the relationship between the human complement cascade and retrovirus inactivation. Preinc...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.4-429
更新日期:1995-04-01 00:00:00
abstract::Replication-deficient adenoviruses are known to induce acute injury and inflammation of infected tissues, thus limiting their use for human gene therapy. However, molecular mechanisms triggering this response have not been fully defined. To characterize this response, chemokine expression was evaluated in DBA/2 mice f...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018364
更新日期:1999-04-10 00:00:00
abstract::Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector e...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.10-1487
更新日期:1998-07-01 00:00:00
abstract::Traditionally, skeletal muscle and liver are the preferred target organs for gene transfer to supply a transgene product into the systemic circulation. In this respect, adipose tissue presents a number of attractive features. However, adipose tissue transduction in vivo has not been feasible by conventional methods. T...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.921
更新日期:2006-09-01 00:00:00
abstract::Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
abstract::Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the comb...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.798
更新日期:2006-08-01 00:00:00
abstract::Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.005
更新日期:2007-04-01 00:00:00
abstract::Vectors derived from the human parvovirus AAV-2 (adeno-associated virus type 2) are among the most promising gene delivery vehicles currently being developed. These vectors are not only capable of transducing a large variety of human cell types in vitro and in vivo, but in immunocompetent animal models can establish l...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/10430349950016799
更新日期:1999-10-10 00:00:00
abstract::Targeted vectors provide a number of advantages for systemic and local gene delivery strategies. Several groups have investigated the utility of using various ligands to alter the tropism of adenovirus (Ad) vectors. We have previously demonstrated that fibroblast growth factor (FGF) ligands can specifically target DNA...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050016265
更新日期:2000-01-01 00:00:00
abstract::Recombinant adeno-associated virus 2 (rAAV2) has been extensively used as a gene delivery vector for the nervous system. It targets primarily neurons in the nervous system and results in sustained long-term expression of transgenes. New rAAV serotypes have been characterized and demonstrated to have improved transduct...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.781
更新日期:2005-07-01 00:00:00
abstract::The hepatocarcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg IIIalpha, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.153
更新日期:2008-09-01 00:00:00
abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.4-487
更新日期:1998-03-01 00:00:00
abstract::Adenovirus-based vectors comprise the most frequently used vector type in clinical studies to date. Both intense lab research and insights from the clinical trials reveal the importance of a comprehensive understanding of vector-host interactions. Especially for systemic intravenous adenovirus vector delivery, it is p...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.139
更新日期:2017-10-01 00:00:00