The Experts below are selected from a list of 37668 Experts worldwide ranked by ideXlab platform
Yahia Chebloune - One of the best experts on this subject based on the ideXlab platform.
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A novel non-integrative single-cycle chimeric HIV lentivector DNA Vaccine
Vaccine, 2015Co-Authors: Maha Moussa, Geraldine Arrode-bruses, Iliyan Manoylov, Alexander Malogolovkin, Dimitri Mompelat, Honorine Ishimwe, Amel Smaoune, Bilel Ouzrout, Jean Gagnon, Yahia CheblouneAbstract:Novel HIV Vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA Vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA Vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of Vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA Vaccine "CAL-SHIV-IN-" that undergoes a single round of replication in the absence of integration resulting in augmented expression of Vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this Vaccine prototype was increased by the removal of the integrase coding sequences from the pal gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN- DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the Vaccine. A single dose DNA immunization of humanized NOD/SCID/beta 2 mice showed a substantial increase of IFN-gamma-ELISPOT in splenocytes compared to the former replication and integration defective Delta 4SHIV-KU2 DNA Vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
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A novel non-integrative single-cycle chimeric HIV lentivector DNA Vaccine
Vaccine, 2015Co-Authors: Maha Moussa, Geraldine Arrode-bruses, Iliyan Manoylov, Alexander Malogolovkin, Dimitri Mompelat, Honorine Ishimwe, Amel Smaoune, Bilel Ouzrout, Jean Gagnon, Yahia CheblouneAbstract:Novel HIV Vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA Vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA Vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of Vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA Vaccine "CAL-SHIV-IN-" that undergoes a single round of replication in the absence of integration resulting in augmented expression of Vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this Vaccine prototype was increased by the removal of the integrase coding sequences from the pal gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN- DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the Vaccine. A single dose DNA immunization of humanized NOD/SCID/beta 2 mice showed a substantial increase of IFN-gamma-ELISPOT in splenocytes compared to the former replication and integration defective Delta 4SHIV-KU2 DNA Vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
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Immunoprophylaxis against AIDS in macaques with a lentiviral DNA Vaccine
Virology, 2006Co-Authors: Zhen Quian Liu, Dinesh K. Singh, Darlene Sheffer, Marilyn S. Smith, Sukhbir Dhillon, Yahia Chebloune, Ramakrishna Hegde, Shilpa Buch, Opendra NarayanAbstract:We earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIVKU2 (Delta rtSHIV(KU2)) plasmid that contained HIV-1 (HXB2) env and SIV gag-nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from Delta rtSHrV(KU2) and substituted the 3'LTR with SV40 poly A sequences, creating Delta 4SHIV(KU2) (M) and a parallel construct containing gag-nef of HIV-1(SF2), Delta 4SHIV(KU2) (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA Vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays. Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA Vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA Vaccine induced broad-based protection without using viral proteins to boost the immunity.
Douglas G Mcneel - One of the best experts on this subject based on the ideXlab platform.
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abstract b147 randomized phase ii trial of a DNA Vaccine encoding prostatic acid phosphatase pap in patients with recurrent prostate cancer nct01341652
Cancer immunology research, 2016Co-Authors: Douglas G Mcneel, Lawrence Fong, Emmanuel S Antonarakis, Glenn LiuAbstract:Background: Patients with rapidly rising PSA alone after definitive therapy for prostate cancer are at high risk for metastatic progression and ultimately death from prostate cancer. This is a stage of disease for which there are no standard therapies, although androgen deprivation is often used. We have previously reported that a DNA Vaccine encoding PAP (pTVG-HP) was safe and could elicit antigen-specific CD4+ and CD8+ T cells in this population (NCT00582140). Patients who developed persistent Th1-type immunity tended to have favorable changes in serum PSA doubling time. The safety, immunological activity, and changes in PSA doubling time were observed in a second pilot clinical trial evaluating different schedules of administration (NCT00849121). Methods: 106 patients with high-risk PSA-recurrent prostate cancer, PSA doubling time Results: To our knowledge, this is the first randomized, phase II trial using an anti-tumor DNA Vaccine. Enrollment is ongoing, but expected to be complete in 2015. The clinical and biomarker plan of evaluation will be presented, as well as descriptions of other pilot clinical trials ongoing with this DNA Vaccine. Citation Format: Douglas G. McNeel, Lawrence Fong, Emmanuel S. Antonarakis, Glenn Liu. Randomized phase II trial of a DNA Vaccine encoding prostatic acid phosphatase (PAP) in patients with recurrent prostate cancer (NCT01341652). [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B147.
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plasmid DNA Vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen specific cd8 t cells
Cancer Immunology Immunotherapy, 2007Co-Authors: Laura E Johnson, Thomas Frye, Nachimuthu Chinnasamy, Dhanalakshmi Chinnasamy, Douglas G McneelAbstract:Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies indicated that Copenhagen rats immunized with a recombinant vaccinia virus expressing human PAP (hPAP) developed PAP-specific cytotoxic T cells (CTL) with cross reactivity to rat PAP (rPAP) and evidence of prostate inflammation. Viral delivery of Vaccine antigens is an active area of clinical investigation. However, a potential difficulty with viral-based immunizations is that immune responses elicited to the viral vector might limit the possibility of multiple immunizations. In this paper, we investigate the ability of another genetic immunization method, a DNA Vaccine encoding PAP, to elicit antigen-specific CD8+ T cell immune responses. Specifically, Lewis rats were immunized with either a plasmid DNA-based (pTVG-HP) or vaccinia-based (VV-HP) Vaccine each encoding hPAP. We determined that rats immunized with a DNA Vaccine encoding hPAP developed a Th1-biased immune response as indicated by proliferating PAP-specific CD4+ and CD8+ cells and IFNγ production. Rats immunized with vaccinia virus encoding PAP did not develop a PAP-specific response unless boosted with a heterologous vaccination scheme. Most importantly, multiple immunizations with a DNA Vaccine encoding the rat PAP homologue (pTVG-RP) could overcome peripheral self-tolerance against rPAP and generate a Th1-biased antigen-specific CD4+ and CD8+ T cell response. Overall, DNA Vaccines provide a safe and effective method of generating prostate antigen-specific T cell responses. These findings support the investigation of PAP-specific DNA Vaccines in human clinical trials.
Deborah H Fuller - One of the best experts on this subject based on the ideXlab platform.
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therapeutic conserved elements ce DNA Vaccine induces strong t cell responses against highly conserved viral sequences during simian human immunodeficiency virus infection
Human Vaccines & Immunotherapeutics, 2018Co-Authors: Paul Munson, Debra Bratt, James T Fuller, Xintao Hu, George N Pavlakis, Barbara K Felber, James I Mullins, Deborah H FullerAbstract:HIV-specific T-cell responses play a key role in controlling HIV infection, and therapeutic Vaccines for HIV that aim to improve viral control will likely need to improve on the T-cell responses induced by infection. However, in the setting of chronic infection, an effective therapeutic Vaccine must overcome the enormous viral genetic diversity and the presence of pre-existing T-cell responses that are biased toward immunodominant T-cell epitopes that can readily mutate to evade host immunity and thus potentially provide inferior protection. To address these issues, we investigated a novel, epidermally administered DNA Vaccine expressing SIV capsid (p27Gag) homologues of highly conserved elements (CE) of the HIV proteome in macaques experiencing chronic but controlled SHIV infection. We assessed the ability to boost or induce de novo T-cell responses against the conserved but immunologically subdominant CE epitopes. Two groups of animals were immunized with either the CE DNA Vaccine or a full-length SIV p57gag DNA Vaccine. Prior to vaccination, CE responses were similar in both groups. The full-length p57gag DNA Vaccine, which contains the CE, increased overall Gag-specific responses but did not increase CE responses in any animals (0/4). In contrast, the CE DNA Vaccine increased CE responses in all (4/4) vaccinated macaques. In SIV infected but unvaccinated macaques, those that developed stronger CE-specific responses during acute infection exhibited lower viral loads. We conclude that CE DNA vaccination can re-direct the immunodominance hierarchy towards CE in the setting of attenuated chronic infection and that induction of these responses by therapeutic vaccination may improve immune control of HIV.
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induction of mucosal protection against primary heterologous simian immunodeficiency virus by a DNA Vaccine
Journal of Virology, 2002Co-Authors: Deborah H Fuller, Joel R Haynes, James T Fuller, Premeela A Rajakumar, Lawrence A Wilson, Anita Trichel, Tim Shipley, Kathleen Weis, Charles R Rinaldo, Michael MurpheycorbAbstract:An effective Vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated Vaccines, the immunogenicity and protective efficacy of a DNA Vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the Vaccine strain. Four of seven Vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable Vaccine approach. These results support further development of a DNA Vaccine for protection against HIV.
Maha Moussa - One of the best experts on this subject based on the ideXlab platform.
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A novel non-integrative single-cycle chimeric HIV lentivector DNA Vaccine
Vaccine, 2015Co-Authors: Maha Moussa, Geraldine Arrode-bruses, Iliyan Manoylov, Alexander Malogolovkin, Dimitri Mompelat, Honorine Ishimwe, Amel Smaoune, Bilel Ouzrout, Jean Gagnon, Yahia CheblouneAbstract:Novel HIV Vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA Vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA Vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of Vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA Vaccine "CAL-SHIV-IN-" that undergoes a single round of replication in the absence of integration resulting in augmented expression of Vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this Vaccine prototype was increased by the removal of the integrase coding sequences from the pal gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN- DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the Vaccine. A single dose DNA immunization of humanized NOD/SCID/beta 2 mice showed a substantial increase of IFN-gamma-ELISPOT in splenocytes compared to the former replication and integration defective Delta 4SHIV-KU2 DNA Vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
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A novel non-integrative single-cycle chimeric HIV lentivector DNA Vaccine
Vaccine, 2015Co-Authors: Maha Moussa, Geraldine Arrode-bruses, Iliyan Manoylov, Alexander Malogolovkin, Dimitri Mompelat, Honorine Ishimwe, Amel Smaoune, Bilel Ouzrout, Jean Gagnon, Yahia CheblouneAbstract:Novel HIV Vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA Vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA Vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of Vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA Vaccine "CAL-SHIV-IN-" that undergoes a single round of replication in the absence of integration resulting in augmented expression of Vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this Vaccine prototype was increased by the removal of the integrase coding sequences from the pal gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN- DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the Vaccine. A single dose DNA immunization of humanized NOD/SCID/beta 2 mice showed a substantial increase of IFN-gamma-ELISPOT in splenocytes compared to the former replication and integration defective Delta 4SHIV-KU2 DNA Vaccine. (C) 2015 Elsevier Ltd. All rights reserved.
Yongqun He - One of the best experts on this subject based on the ideXlab platform.
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DNAVaxDB: the first web-based DNA Vaccine database and its data analysis
BMC Bioinformatics, 2014Co-Authors: Rebecca Racz, Xinna Li, Mukti Patel, Zuoshuang Xiang, Yongqun HeAbstract:Since the first DNA Vaccine studies were done in the 1990s, thousands more studies have followed. Here we report the development and analysis of DNAVaxDB ( http://www.violinet.org/DNAvaxdb ), the first publically available web-based DNA Vaccine database that curates, stores, and analyzes experimentally verified DNA Vaccines, DNA Vaccine plasmid vectors, and protective antigens used in DNA Vaccines. All data in DNAVaxDB are annotated from reliable resources, particularly peer-reviewed articles. Among over 140 DNA Vaccine plasmids, some plasmids were more frequently used in one type of pathogen than others; for example, pCMVi-UB for G- bacterial DNA Vaccines, and pCAGGS for viral DNA Vaccines. Presently, over 400 DNA Vaccines containing over 370 protective antigens from over 90 infectious and non-infectious diseases have been curated in DNAVaxDB. While extracellular and bacterial cell surface proteins and adhesin proteins were frequently used for DNA Vaccine development, the majority of protective antigens used in Chlamydophila DNA Vaccines are localized to the inner portion of the cell. The DNA Vaccine priming, other Vaccine boosting vaccination regimen has been widely used to induce protection against infection of different pathogens such as HIV. Parasitic and cancer DNA Vaccines were also systematically analyzed. User-friendly web query and visualization interfaces are available in DNAVaxDB for interactive data search. To support data exchange, the information of DNA Vaccines, plasmids, and protective antigens is stored in the Vaccine Ontology (VO). DNAVaxDB is targeted to become a timely and vital source of DNA Vaccines and related data and facilitate advanced DNA Vaccine research and development.