Abstract:
:Adeno-associated virus (AAV) vectors are one of the most efficient in vivo gene delivery platforms. Over the past decade, clinical trials of AAV vector-mediated gene transfer led to some of the most exciting results in the field of gene therapy and, recently, to the market approval of an AAV-based drug in Europe. With clinical development, however, it became obvious that the host immune system represents an important obstacle to successful gene transfer with AAV vectors. In this review article, we will discuss the issue of cytotoxic T cell responses directed against the AAV capsid encountered on human studies. While over the past several years the field has acquired a tremendous amount of information on the interactions of AAV vectors with the immune system, a lot of questions are still unanswered. Novel concepts are emerging, such as the relationship between the total capsid dose and the T cell-mediated clearance of transduced cells, the potential role of innate immunity in vector immunogenicity highlighted in preclinical studies, and the cross talk between regulatory and effector T cells in the determination of the outcome of gene transfer. There is still a lot to learn about immune responses in AAV gene transfer, for example, it is not well understood what are the determinants of the kinetics of activation of T cells in response to vector administration, why not all subjects develop detrimental T cell responses following gene transfer, and whether the intervention strategies currently in use to block T cell-mediated clearance of transduced cells will be safe and effective for all gene therapy indications. Results from novel preclinical models and clinical studies will help to address these points and to reach the important goal of developing safe and effective gene therapy protocols to treat human diseases.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Basner-Tschakarjan E,Mingozzi Fdoi
10.3389/fimmu.2014.00350subject
Has Abstractpub_date
2014-07-23 00:00:00pages
350issn
1664-3224journal_volume
5pub_type
杂志文章,评审abstract::Acinetobacter baumannii (A. baumannii) is becoming a common global concern due to the emergence of multi-drug or pan-drug resistant strains. Confronting the issue of antimicrobial resistance by developing vaccines against the resistant pathogen is becoming a common strategy. In this study, different methods for prepar...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01069
更新日期:2020-06-23 00:00:00
abstract::Immunotherapies that can either activate or suppress innate immune responses are being investigated as treatments against infectious diseases and the pathology they can cause. The objective of these therapies is to elicit protective immune responses thereby limiting the harm inflicted by the pathogen. The Toll-like re...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00079
更新日期:2014-03-03 00:00:00
abstract::Extrapulmonary tuberculosis (EPTB) has become more common in recent years; however, the diagnosis of EPTB remains a challenge. In this study, we analyzed the performance of the ratio of TB-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT.TB (T-SPOT) assay for diagnosis and treatment monit...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01047
更新日期:2018-05-14 00:00:00
abstract::Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into sy...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00465
更新日期:2019-03-18 00:00:00
abstract:Background:The role of the lectin pathway of complement in the pathogenesis of interstitial lung diseases (ILDs) is largely unknown. Pattern recognition receptors (PRR) of the lectin pathway are involved in the clearance of apoptotic cells either via activation of the complement system or as direct opsonins. As recent ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.562564
更新日期:2020-09-23 00:00:00
abstract::Controversy over the frequency of human B1 cells in normal individuals has arisen as different labs have begun to employ non-uniform techniques to study this population. The phenotypic profile and relative paucity of circulating human B1 cells place constraints on methodology to identify and isolate this population. M...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00122
更新日期:2012-05-25 00:00:00
abstract::Understanding affinity maturation of antibodies that can target many variants of HIV-1 is important for vaccine development. While the antigen-binding site of antibodies is known to mutate throughout the co-evolution of antibodies and viruses in infected individuals, the roles of the mutations in the antibody framewor...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01529
更新日期:2020-07-17 00:00:00
abstract::Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer thera...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00072
更新日期:2019-01-29 00:00:00
abstract::The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses. However, these approach...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00040
更新日期:2016-02-16 00:00:00
abstract::Due to limited sepsis patient cohort size and extreme heterogeneity, only one significant locus and suggestive associations at several independent loci were implicated by three genome-wide association studies. However, genes from such suggestive loci may also provide crucial information to unravel genetic mechanisms t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01949
更新日期:2019-08-14 00:00:00
abstract:Background:The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many in vitro studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechan...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00634
更新日期:2018-04-04 00:00:00
abstract::Macrophages are heterogeneous leukocytes regulated in a tissue- and disease-specific context. While in vitro macrophage models have been used to study diseases empirically, a systematic analysis of the transcriptome thereof is lacking. Here, we acquired gene expression data from eight commonly-used in vitro macrophage...
journal_title:Frontiers in immunology
pub_type: 杂志文章,meta分析
doi:10.3389/fimmu.2019.02887
更新日期:2019-12-11 00:00:00
abstract::The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infe...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02133
更新日期:2020-09-02 00:00:00
abstract::Human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have become a useful clinical biomarker for the diagnosis of a spectrum of inflammatory demyelinating disorders. Live cell-based assays that detect MOG Ab against conformational MOG are currently the gold standard. Flow cytometry, in which ser...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00119
更新日期:2020-02-06 00:00:00
abstract::Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the un...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02647
更新日期:2018-11-14 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) can be divided into prognostically distinct subsets with stereotyped or non-stereotyped, mutated or unmutated B cell receptors (BCRs). Individual subsets vary in antigen specificity and origin, but the impact of antigenic pressure on the CLL BCR repertoire remains unknown. Here, we e...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01996
更新日期:2018-09-13 00:00:00
abstract::The salivary scavenger and agglutinin (SALSA), also known as gp340, salivary agglutinin and deleted in malignant brain tumor 1, is a 340-kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00205
更新日期:2012-07-16 00:00:00
abstract::Earlier data suggest that progesterone-induced blocking factor (PIBF) is involved in implantation. The present study therefore aims to investigate the consequences of functional PIBF deficiency during the peri-implantation period. CD1 female mice were injected intraperitoneally with 2 μg anti-PIBF monoclonal antibody ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00349
更新日期:2020-03-11 00:00:00
abstract::Currently, inflammatory bowel disease (IBD) is a serious public health problem on the rise worldwide. In this work, we utilized the zebrafish to introduce a new model of intestinal inflammation triggered by food intake. Taking advantage of the translucency of the larvae and the availability of transgenic zebrafish lin...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00610
更新日期:2019-04-02 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2018.00707.]. ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,已发布勘误
doi:10.3389/fimmu.2018.02218
更新日期:2018-09-27 00:00:00
abstract::IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circul...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00267
更新日期:2020-02-28 00:00:00
abstract::Recent studies have identified CD49a+Eomes- and CD49a+Eomes+ subsets of tissue-resident NK (trNK) cells in different organs of the mouse. However, the characteristics of CD49a+Eomes-/+ NK cell development and the regulation of Eomes expression in NK cells remain unclear. Here, we established an in vitro cytokine-based...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02126
更新日期:2018-09-25 00:00:00
abstract::Keloids are disfiguring, fibroproliferative growths and their pathogenesis remains unclear, inhibiting therapeutic development. Available treatment options have limited efficacy and harbor safety concerns. Thus, there is a great need to clarify keloid pathomechanisms that may lead to novel treatments. In this study, w...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.597741
更新日期:2020-11-23 00:00:00
abstract::Neddylation is a type of post-translational protein modifications, in which neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently conjugated to the lysine residues of target substrates. The best characterized principal substrates of neddylation are the cullin-RING ligases (CRLs)...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01432
更新日期:2019-06-25 00:00:00
abstract::Vγ9Vδ2-T cells are considered as potent effector cells for tumor immunotherapy through directly killing tumor cells and indirectly regulating other innate and adaptive immune cells to establish antitumoral immunity. The antitumoral activity of Vγ9Vδ2-T cells is governed by a complicated set of activating and inhibitor...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01041
更新日期:2017-08-28 00:00:00
abstract::The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the inc...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01821
更新日期:2018-08-10 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2019.00702.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2020.592865
更新日期:2020-10-28 00:00:00
abstract::Mycobacterium tuberculosis continues to be one of the most successful pathogens on earth. Upon inhalation of M. tuberculosis by a healthy individual, the host immune system will attempt to eliminate these pathogens using a combination of immune defense strategies. These include the recruitment of macrophages and other...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00455
更新日期:2014-10-08 00:00:00
abstract::Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (-)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenu...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00433
更新日期:2017-04-10 00:00:00
abstract::Clinical management of neuropathic pain is unsatisfactory, mainly due to its resistance to the effects of available analgesics, including opioids. Converging evidence indicates the functional interactions between chemokine and opioid receptors and their influence on nociceptive processes. Recent studies highlight that...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.615327
更新日期:2020-12-21 00:00:00