Genetic Immunity

Budapest, Hungary

Genetic Immunity

Budapest, Hungary
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De Filette M.,Ghent University | Soehle S.,University of Zürich | Ulbert S.,Fraunhofer Institute for Cell Therapy and Immunology | Richner J.,University of Washington | And 7 more authors.
PLoS ONE | Year: 2014

West Nile virus (WNV) is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI) covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime - boost regime) with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical). In parallel a heterologous boost with purified recombinant WNV envelope (E) protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection. © 2014 De Filette et al.


PubMed | University of Padua, University of Washington, Fraunhofer Institute for Cell Therapy and Immunology, University of Zürich and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2014

West Nile virus (WNV) is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI) covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime--boost regime) with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical). In parallel a heterologous boost with purified recombinant WNV envelope (E) protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8(+) specific IFN- expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.


Somogyi E.,Genetic Immunity | Xu J.,Research Institute for Genetic and Human Therapy | Xu J.,Fudan University | Gudics A.,Genetic Immunity | And 4 more authors.
Vaccine | Year: 2011

We describe here a single plasmid DNA immunogen representing the broadest antigen repertoire among HIV vaccine candidates. This pDNA was "ANTIGENeered" for the regulated expression of thirteen complete and two non-functional HIV protein antigens. These proteins self assemble into complex virus-like particles (VLP+). Multiple irreversible safety features were introduced by genetic modifications including the complete impairment of integration, reverse transcription, the function of Nef and the 3'LTR. Epitope analysis predicted that the pDNA-derived protein repertoire can potentially present over 3000 T cell epitopes. However, the expressed antigens have different potential to induce HIV-specific CD4+ and CD8+ T cells supporting our hypothesis that HIV vaccines should contain all possible regulatory and structural proteins. This immunogen is the active pharmaceutical ingredient of DermaVir, a therapeutic vaccine product candidate that recently successfully completed Phase II clinical trials and meets the safety, immunogenicity and cost requirements of an HIV vaccine. © 2010 Elsevier Ltd.


Garaczi E.,University of Szeged | Szabo K.,University of Szeged | Francziszti L.,University of Szeged | Csiszovszki Z.,Genetic Immunity | And 14 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2013

Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases. From the Clinical Editor: A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses. © 2013 Elsevier Inc.


Kolonics A.,Hungarian Academy of Sciences | Kolonics A.,R and D Ultrafast Lasers Ltd | Csiszovszki Z.,Genetic Immunity | Toke E.,R and D Ultrafast Lasers Ltd | And 7 more authors.
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 | Year: 2013

Fluorescently labelled polyethylenimine-mannose/DNA nanoparticles caused morphological and intracellular changes in Langerhans cells as studied by multiphoton laser microscopy in vivo in ear of knock-in mice expressing enhanced Green Fluorescent Protein under control of langerin gene. ©2013 The Optical Society (OSA).


Lisziewicz J.,Genetic Immunity | Szebeni J.,Semmelweis University
European Journal of Nanomedicine | Year: 2010

Nanomedicines are pharmaceutical agents consisting of ∼20-400 nm size particles that overlap with the size of viruses and, hence, are recognized by the immune system. The resulting stimulation of the innate and antigen-specific immune responses can be either beneficial or harmful. This review focuses on two examples of the Janus faced interaction between the nanomedicines and the immune system; the beneficial stimulation of epidermal Langerhans cells and expansion of HIV-specific memory T cells by a therapeutic AIDS vaccine (DermaVir), and the harmful triggering of the complement (C) system leading to hypersensitivity reactions, called C activation related pseudoallergy (CARPA). In addition to the illustrated survey of the molecular-cellular interactions underlying these phenomena, this review provides an update on the clinical development of DermaVir and the state of CARPA prevention - anti-CARPA therapy.


Gudics A.,Genetic Immunity | Lisziewicz J.,Genetic Immunity
European Journal of Nanomedicine | Year: 2010

Active immunotherapies against tumors and viruses have to induce functional memory CTLs that requires the activation of naïve T cells by dendritic cells (DC). Sipuleucel-T, the first cancer immunotherapeutic product expected to create new treatment paradigm, employs transplantation of ex vivo cultured DCs. To improve the clinical benefits and reduce the costs of ex vivo therapies, in vivo DC loading nanomedicine technologies are under development. These DC-based nanomedicine products must overcome the complex problems of receptor targeting and uptake of the antigen, maturation and migration of DCs to the lymphoid organs, antigen processing and presentation to naïve T cells. The combination of two new technologies, antigen nanoformulation and topical DermaPrep administration, has shown to target antigens in vivo to lymph nodes by a subset of epidermal DC leading to the induction of functional memory T cells. This DC-targeting nanomedicine platform technology has been developed for the treatment of infectious diseases and cancers, including HIV/AIDS.


Evaluation of: Pleguezuelos O, Stoloff GA, Caparros-Wanderley W. Synthetic immunotherapy induces HIV virus specific Th1 cytotoxic response and death of an HIV-1 infected human cell line through classic complement activation. Virol. J. 10(1), 107 (2013). AIDS vaccine development represents an unprecedented challenge in both immunogen design and delivery to induce potent and long-lasting HIV-specific immune responses, including neutralizing antibodies and cytotoxic T lymphocytes (CTL). Pleguezuelos and coworkers recognized that immunogen design must address both HIV and HLA diversity to make a global vaccine. The HIV-v synthetic polypeptide vaccine described here sets a new standard in antigen design by selecting conserved regions of global HIV-1 and HIV-2 isolates and epitopes from most frequent HLA types of the human population. The new vaccine induced both antibody and CTL responses. Importantly, the authors demonstrated vaccine-specific HLA restricted CD8 + CTL responses for one HLA allele that was involved in the antigen design. HIV-v vaccine is a new candidate to be tested in human subjects carrying frequent HLA types. © 2013 Future Medicine Ltd.

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