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https://www.readbyqxmd.com/read/27834857/the-cd8%C3%A2-%C2%BA-t-cell-mediated-immunity-induced-by-hpv-e6-uploaded-in-engineered-exosomes-is-improved-by-iscomatrix-tm-adjuvant
#1
Francesco Manfredi, Paola di Bonito, Barbara Ridolfi, Simona Anticoli, Claudia Arenaccio, Chiara Chiozzini, Adriana Baz Morelli, Maurizio Federico
We recently described the induction of an efficient CD8⁺ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8⁺ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8⁺ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting...
November 9, 2016: Vaccines
https://www.readbyqxmd.com/read/27634183/an-updated-review-of-iscoms-tm-and-iscomatrix-tm-vaccines
#2
Alexis Garcia, Diego Lema
The need for the improvement of vaccine potency as well as reducing toxicity in healthy recipients has motivated studies of the formulation of vaccines regarding control of how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following vaccine administration. Immunostimulatory complexes (ISCOMs) and ISCOMATRIX<sup>TM</sup> adjuvants are versatile and flexible systems with various phospholipids and saponin components. They are being used in novel vaccines for either infectious diseases or cancer...
September 15, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27149269/meta-analysis-on-randomized-controlled-trials-of-vaccines-with-qs-21-or-iscomatrix-adjuvant-safety-and-tolerability
#3
Emilia Bigaeva, Eva van Doorn, Heng Liu, Eelko Hak
BACKGROUND AND OBJECTIVES: QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. METHODS: A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes...
2016: PloS One
https://www.readbyqxmd.com/read/27081463/the-role-of-iscomatrix-bilayer-composition-to-induce-a-cell-mediated-immunity-and-protection-against-leishmaniasis-in-balb-c-mice
#4
Ahmad Mehravaran, Mahmoud Reza Jaafari, Seyed Amir Jalali, Ali Khamesipour, Reza Ranjbar, Mansure Hojatizade, Ali Badiee
OBJECTIVES: Development of new generation of vaccines against leishmaniasis is possible because long-term protection is usually seen after recovery from cutaneous leishmaniasis. ISCOMATRIX is particulate antigen delivery system composed of antigen, cholesterol, phospholipid and saponin. In this study, the role of ISCOMATRIX bilayer composition made by different phase transition temperature (Tc) to induce a type of immune response and protection against leishmaniasis was assessed. MATERIALS AND METHODS: ISCOMATRIX formulations with different bilayer compositions consisting of EPC (Tc <0 °C), DMPC (Tc 23 °C) and DSPC (Tc 54 °C) were prepared...
February 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/26647717/induction-of-partial-immunity-in-both-males-and-females-is-sufficient-to-protect-females-against-sexual-transmission-of-chlamydia
#5
C P O'Meara, C W Armitage, A Kollipara, D W Andrew, L Trim, M B Plenderleith, K W Beagley
Sexually transmitted Chlamydia trachomatis causes infertility, and because almost 90% of infections are asymptomatic, a vaccine is required for its eradication. Mathematical modeling studies have indicated that a vaccine eliciting partial protection (non-sterilizing) may prevent Chlamydia infection transmission, if administered to both sexes before an infection. However, reducing chlamydial inoculum transmitted by males and increasing infection resistance in females through vaccination to elicit sterilizing immunity has yet to be investigated experimentally...
July 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/26458804/preclinical-and-clinical-development-of-a-dengue-recombinant-subunit-vaccine
#6
REVIEW
Susan B Manoff, Sarah L George, Andrew J Bett, Michele L Yelmene, Govindarajan Dhanasekaran, Linda Eggemeyer, Michele L Sausser, Sheri A Dubey, Danilo R Casimiro, David E Clements, Timothy Martyak, Vidya Pai, D Elliot Parks, Beth-Ann G Coller
This review focuses on a dengue virus (DENV) vaccine candidate based on a recombinant subunit approach which targets the DENV envelope glycoprotein (E). Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) have been expressed recombinantly in the Drosophila S2 expression system and shown to have native-like conformation. Preclinical studies demonstrate that formulations containing tetravalent DEN-80E adjuvanted with ISCOMATRIX™ adjuvant induce high titer virus neutralizing antibodies and IFN-γ producing T cells in flavivirus-naïve non-human primates...
December 10, 2015: Vaccine
https://www.readbyqxmd.com/read/26144900/preclinical-development-of-a-dengue-tetravalent-recombinant-subunit-vaccine-immunogenicity-and-protective-efficacy-in-nonhuman-primates
#7
Dhanasekaran Govindarajan, Steven Meschino, Liming Guan, David E Clements, Jan H ter Meulen, Danilo R Casimiro, Beth-Ann G Coller, Andrew J Bett
We describe here the preclinical development of a dengue vaccine composed of recombinant subunit carboxy-truncated envelope (E) proteins (DEN-80E) for each of the four dengue serotypes. Immunogenicity and protective efficacy studies in Rhesus monkeys were conducted to evaluate monovalent and tetravalent DEN-80E vaccines formulated with ISCOMATRIX™ adjuvant. Three different doses and two dosing regimens (0, 1, 2 months and 0, 1, 2, and 6 months) were evaluated in these studies. We first evaluated monomeric (DEN4-80E) and dimeric (DEN4-80EZip) versions of DEN4-80E, the latter generated in an attempt to improve immunogenicity...
August 7, 2015: Vaccine
https://www.readbyqxmd.com/read/26093202/iscomatrix%C3%A2-adjuvant-promotes-epitope-spreading-and-antibody-affinity-maturation-of-influenza-a-h7n9-virus-like-particle-vaccine-that-correlate-with-virus-neutralization-in-humans
#8
Ka Yan Chung, Elizabeth M Coyle, Dewal Jani, Lisa R King, Rukmini Bhardwaj, Louis Fries, Gale Smith, Gregory Glenn, Hana Golding, Surender Khurana
In a previously reported phase I clinical trial, subjects vaccinated with two doses of an unadjuvanted H7N9 virus like particle (VLP) vaccine responded poorly (15.6% seroconversion rates with 45μg hemagglutinin (HA) dose). In contrast, 80.6% of subjects receiving H7N9 VLP vaccine (5μg HA) with ISCOMATRIX™ adjuvant developed hemagglutination-inhibition (HI) responses. To better understand the role of adjuvant, complete antibody epitope repertoires of post-vaccination sera were investigated using Whole Genome Fragment Phage Display Library (GFPDL)...
July 31, 2015: Vaccine
https://www.readbyqxmd.com/read/25772674/recombinant-virus-like-particles-elicit-protective-immunity-against-avian-influenza-a-h7n9-virus-infection-in-ferrets
#9
Ye V Liu, Michael J Massare, Melissa B Pearce, Xiangjie Sun, Jessica A Belser, Taronna R Maines, Hannah M Creager, Gregory M Glenn, Peter Pushko, Gale E Smith, Terrence M Tumpey
In March 2013, diagnosis of the first reported case of human infection with a novel avian-origin influenza A(H7N9) virus occurred in eastern China. Most human cases have resulted in severe respiratory illness and, in some instances, death. Currently there are no licensed vaccines against H7N9 virus, which continues to cause sporadic human infections. Recombinant virus-like particles (VLPs) have been previously shown to be safe and effective vaccines for influenza. In this study, we evaluated the immunogenicity and protective efficacy of a H7N9 VLP vaccine in the ferret challenge model...
April 27, 2015: Vaccine
https://www.readbyqxmd.com/read/25692970/iscomatrix%C3%A2-adjuvant-reduces-mucosal-tolerance-for-effective-pulmonary-vaccination-against-influenza
#10
Andrea A Timothy, Ana Tokanovic, Kenneth J Snibson, Stirling J Edwards, Martin J Pearse, Jean-Pierre Y Scheerlinck, Philip Sutton
While most pathogens infect via mucosal surfaces, most current vaccines are delivered by injection. This situation remains despite awareness of the potential benefits of mucosal delivery for inducing protection against mucosa-infecting pathogens. A major obstacle to the development of such vaccines is the paucity of safe and effective adjuvants that induce mucosal responses in non-rodents. Previously we demonstrated in sheep the potency of pulmonary-delivered influenza ISCOMATRIX™ vaccine, which induces both mucosal and systemic immunity, even with low antigen doses...
2015: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/25662405/low-dose-cyclophosphamide-enhances-antigen-specific-cd4-t-cell-responses-to-ny-eso-1-iscomatrix%C3%A2-vaccine-in-patients-with-advanced-melanoma
#11
MULTICENTER STUDY
Oliver Klein, Ian D Davis, Grant A McArthur, Li Chen, Andrew Haydon, Phillip Parente, Nektaria Dimopoulos, Heather Jackson, Kun Xiao, Eugene Maraskovsky, Wendie Hopkins, Rodica Stan, Weisan Chen, Jonathan Cebon
Clinical outcomes from cancer vaccine trials in patients with advanced melanoma have so far been disappointing. This appears at least partially due to a state of immunosuppression in these patients induced by an expansion of regulatory cell populations including regulatory T cells (Tregs). We have previously demonstrated potent immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine in patients with resected melanoma (study LUD99-08); however, the same vaccine induced only a few vaccine antigen-specific immune responses in patients with advanced disease (study LUD2002-013)...
April 2015: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/25646304/the-combination-of-iscomatrix-adjuvant-and-tlr-agonists-induces-regression-of-established-solid-tumors-in-vivo
#12
Anabel Silva, Adele Mount, Karoline Krstevska, David Pejoski, Matthew P Hardy, Catherine Owczarek, Pierre Scotney, Eugene Maraskovsky, Adriana Baz Morelli
The development of therapeutic vaccines for treatment of established cancer has proven challenging. Cancer vaccines not only need to induce a robust tumor Ag-specific immune response but also need to overcome the tolerogenic and immunosuppressive microenvironments that exist within many solid cancers. ISCOMATRIX adjuvant (ISCOMATRIX) is able to induce both tumor Ag-specific cellular and Ab responses to protect mice against tumor challenge, but this is insufficient to result in regression of established solid tumors...
March 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25625671/efficacy-of-a-trans-sialidase-iscomatrix-subunit-vaccine-candidate-to-protect-against-experimental-chagas-disease
#13
Iván Alejandro Bontempi, Miguel Hernán Vicco, Gabriel Cabrera, Silvina Raquel Villar, Florencia Belén González, Eduardo Angel Roggero, Paul Ameloot, Nico Callewaert, Ana Rosa Pérez, Iván Sergio Marcipar
Recombinant protein vaccines are safe but elicit low immunological responses. The new generation of adjuvants is currently reversing this situation. Here, a new antigen-adjuvant combination for protection against experimental Chagas disease was assessed. The antigen used in the formulation was a glycosylated mutant inactive trans-sialidase (mTS) that was previously proven to be highly protective against Trypanosoma cruzi infection; here, we show that it can be produced in large quantities and high quality using Pichia pastoris...
March 3, 2015: Vaccine
https://www.readbyqxmd.com/read/25081390/ny-eso-1-specific-antibody-and-cellular-responses-in-melanoma-patients-primed-with-ny-eso-1-protein-in-iscomatrix-and-boosted-with-recombinant-ny-eso-1-fowlpox-virus
#14
RANDOMIZED CONTROLLED TRIAL
Ji-Li Chen, Amina Dawoodji, Andrea Tarlton, Sacha Gnjatic, Abdelouahid Tajar, Ioannis Karydis, Judy Browning, Sarah Pratap, Christian Verfaille, Ralph R Venhaus, Linda Pan, Douglas G Altman, Jonathan S Cebon, Lloyd L Old, Paul Nathan, Christian Ottensmeier, Mark Middleton, Vincenzo Cerundolo
Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8(+) or CD4(+) T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B)...
March 15, 2015: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/24610009/inflammasome-dependent-and-independent-il-18-production-mediates-immunity-to-the-iscomatrix-adjuvant
#15
Nicholas S Wilson, Peter Duewell, Becky Yang, Yun Li, Scot Marsters, Sandra Koernig, Eicke Latz, Eugene Maraskovsky, Adriana Baz Morelli, Max Schnurr, Avi Ashkenazi
Adjuvants are an essential component of modern vaccines and used for their ability to elicit immunity to coadministered Ags. Many adjuvants in clinical development are particulates, but how they drive innate and adaptive immune responses remains poorly understood. Studies have shown that a number of vaccine adjuvants activate inflammasome pathways in isolated APCs. However, the contribution of inflammasome activation to vaccine-mediated immunity in vivo remains controversial. In this study, we evaluated immune cell responses to the ISCOMATRIX adjuvant (IMX) in mice...
April 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24513632/reduced-myd88-dependency-of-iscomatrix%C3%A2-adjuvant-in-a-dna-prime-protein-boost-hiv-vaccine
#16
Rachel Buglione-Corbett, Kimberly Pouliot, Robyn Marty-Roix, Wei Li, Kim West, Shixia Wang, Adriana Baz Morelli, Egil Lien, Shan Lu
ISCOMATRIX™ adjuvant is an integrated adjuvant system due to its ability to both facilitate antigen delivery and immunomodulate the innate and adaptive immune responses to vaccination. ISCOMATRIX™ adjuvant strongly induces both humoral and cell-mediated immunity in formulation with a range of antigens in pre-clinical and clinical evaluations. In this study, we describe the adaptive and innate immune responses associated with ISCOMATRIX™ adjuvant in the context of a previously described HIV-1 vaccine, DP6-001...
2014: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/24284325/protection-provided-by-a-herpes-simplex-virus-2-hsv-2-glycoprotein-c-and-d-subunit-antigen-vaccine-against-genital-hsv-2-infection-in-hsv-1-seropositive-guinea-pigs
#17
MULTICENTER STUDY
Sita Awasthi, John W Balliet, Jessica A Flynn, John M Lubinski, Carolyn E Shaw, Daniel J DiStefano, Michael Cai, Martha Brown, Judith F Smith, Rose Kowalski, Ryan Swoyer, Jennifer Galli, Victoria Copeland, Sandra Rios, Robert C Davidson, Maya Salnikova, Susan Kingsley, Janine Bryan, Danilo R Casimiro, Harvey M Friedman
A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum. In study 2, gD2 was produced in CHO cells and given intramuscularly with monophosphoryl lipid A (MPL) and alum, or gC2 and gD2 were produced in glycoengineered Pichia pastoris and administered intramuscularly as a bivalent vaccine with Iscomatrix and alum to HSV-1-naive or -seropositive guinea pigs...
February 2014: Journal of Virology
https://www.readbyqxmd.com/read/24019983/serum-cytokine-profiles-associated-with-specific-adjuvants-used-in-a-dna-prime-protein-boost-vaccination-strategy
#18
Rachel Buglione-Corbett, Kimberly Pouliot, Robyn Marty-Roix, Kim West, Shixia Wang, Egil Lien, Shan Lu
In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine...
2013: PloS One
https://www.readbyqxmd.com/read/23941913/immunogenicity-of-a-reduced-dose-whole-killed-rabies-vaccine-is-significantly-enhanced-by-iscomatrix%C3%A2-adjuvant-merck-amorphous-aluminum-hydroxylphosphate-sulfate-maa-or-a-synthetic-tlr9-agonist-in-rhesus-macaques
#19
Daniel DiStefano, Joseph M Antonello, Andrew J Bett, Muneeswara B Medi, Danilo R Casimiro, Jan ter Meulen
There is a need for novel rabies vaccines suitable for short course, pre- and post-exposure prophylactic regimens which require reduced doses of antigen to address the current worldwide supply issue. We evaluated in rhesus macaques the immunogenicity of a quarter-dose of a standard rabies vaccine formulated with Merck's amorphous aluminum hydroxylphosphate sulfate adjuvant, the saponin-based ISCOMATRIX™ adjuvant, or a synthetic TLR9 agonist. All adjuvants significantly increased the magnitude and durability of the humoral immune response as measured by rapid fluorescent focus inhibition test (RFFIT)...
October 1, 2013: Vaccine
https://www.readbyqxmd.com/read/23891795/development-of-influenza-h7n9-virus-like-particle-vlp-vaccine-homologous-a-anhui-1-2013-h7n9-protection-and-heterologous-a-chicken-jalisco-cpa1-2012-h7n3-cross-protection-in-vaccinated-mice-challenged-with-h7n9-virus
#20
Gale E Smith, David C Flyer, Ramadevi Raghunandan, Ye Liu, Ziping Wei, Yingyun Wu, Eloi Kpamegan, Denise Courbron, Louis F Fries, Gregory M Glenn
The recent emergence of severe human illness caused by avian-origin influenza A(H7N9) viruses in China has precipitated a global effort to rapidly develop and test vaccine candidates. To date, non-A(H7N9) H7 subtype influenza vaccine candidates have been poorly immunogenic and difficulties in production of A(H7N9) virus seed strains have been encountered. A candidate recombinant A(H7N9) vaccine consisting of full length, unmodified hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) were cloned into a baculovirus vector...
September 13, 2013: Vaccine
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