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Shridhar Bale, Alexandra Martiné, Richard Wilson, Anna-Janina Behrens, Valérie Le Fourn, Natalia de Val, Shailendra K Sharma, Karen Tran, Jonathan L Torres, Pierre-Alain Girod, Andrew B Ward, Max Crispin, Richard T Wyatt
Native flexibly linked (NFL) HIV-1 envelope glycoprotein (Env) trimers are cleavage-independent and display a native-like, well-folded conformation that preferentially displays broadly neutralizing determinants. The NFL platform simplifies large-scale production of Env by eliminating the need to co-transfect the precursor-cleaving protease, furin that is required by the cleavage-dependent SOSIP trimers. Here, we report the development of a CHO-M cell line that expressed BG505 NFL trimers at a high level of homogeneity and yields of ~1...
2018: Frontiers in Immunology
Jafar Mosafer, Ali Badiee, Zahra Mohammadamini, Alireza Komeilinezhad, Mohsen Tafaghodi
Chitosan-coated ISCOMATRIX nanoparticles co-administrated with PR8 influenza virus were successfully developed via a lipid film hydration method to evaluate their in vivo immuniadjuvant potential in immunization against influenza. The prepared ISCOMATRIX (ISC) and chitosan-coated ISCOMATRIX (ISC-CIT) showed a particle size of 171 and 233 nm with a zeta potential of -9.47 and +5.65, respectively. Furthermore, ISC-CIT formulations were co-administered with PR8 antigen (PR8-ISC-CIT) and their immunogenicity was investigated after intranasal and intramuscular immunization of BALBc/mice...
April 24, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Ruth Pye, Amanda Patchett, Elspeth McLennan, Russell Thomson, Scott Carver, Samantha Fox, David Pemberton, Alexandre Kreiss, Adriana Baz Morelli, Anabel Silva, Martin J Pearse, Lynn M Corcoran, Katherine Belov, Carolyn J Hogg, Gregory M Woods, A Bruce Lyons
Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government's Wild Devil Recovery project...
2018: Frontiers in Immunology
Silvia Capucci, Edmund G Wee, Torben Schiffner, Celia C LaBranche, Nicola Borthwick, Albert Cupo, Jonathan Dodd, Hansi Dean, Quentin Sattentau, David Montefiori, Per J Klasse, Rogier W Sanders, John P Moore, Tomáš Hanke
Rabbits and monkeys immunized with HIV type 1 (HIV-1) native-like BG505 SOSIP.664 (BG505s) glycoprotein trimers are known to induce antibodies that can neutralize the autologous tier-2 virus. Here, we assessed the induction of HIV-1 trimer binding and neutralizing antibody (nAb) titres when BG505s trimers were also delivered by non-replicating simian (chimpanzee) adenovirus and non-replicating poxvirus modified vaccinia virus Ankara (MVA) vaccine vectors. First, we showed that approximately two-thirds and one-third of the trimers secreted from the ChAdOx1...
2017: PloS One
Daiana Bertona, Nazarena Pujato, Iván Bontempi, Verónica Gonzalez, Gabriel Cabrera, Luis Gugliotta, Daniela Hozbor, Alcides Nicastro, Luis Calvinho, Iván Sergio Marcipar
OBJECTIVES: To obtain and assess stable cage-like particles with low surface charge density, which can be prepared using a standardized, economic and scalable method. METHODS: To form these nanoparticles, the lipid composition and proportion as well the method were modified in relation to cage-like particles previously described elsewhere. Bovine albumin was used to compare ISPA performance with that of other adjuvants in mice and to assess stability. Adjuvant efficacy was analysed using a mouse model of Trypanosoma cruzi infection, which shows protection against an intracellular infection that needs a strong cellular response...
June 30, 2017: Journal of Pharmacy and Pharmacology
Connor P O'Meara, Charles W Armitage, Dean W Andrew, Avinash Kollipara, Nils Y Lycke, Andrew A Potter, Volker Gerdts, Nikolai Petrovsky, Kenneth W Beagley
Pathogens with a complex lifecycles can effectively evade host immunity in part due to each developmental stage expressing unique sets of antigens. Multisubunit vaccines incorporating signature antigens reflecting distinct developmental stages (multistage vaccines) have proven effective against viral, bacterial and parasitic infection at preventing pathogen evasion of host immunity. Chlamydia trachomatis is characterized by a biphasic extra/intracellular developmental cycle and an acute/persistent (latent) metabolic state; hence a multistage vaccine may prevent immune evasion and enhance clearance...
July 5, 2017: Vaccine
Ivan Bontempi, Pedro Fleitas, Alexia Poato, Miguel Vicco, Luz Rodeles, Estefania Prochetto, Gabriel Cabrera, Bruno Beluzzo, Diego Arias, Andrea Racca, Sergio Guerrero, Iván Marcipar
AIM: The development of vaccines against Trypanosoma cruzi remains in an exploratory stage. Despite several antigen candidates have been evaluated, a comparison among the performance of the immunogens cannot be carried out because the available reports differ in formulations and infection model. In this work, we compared the protective capacity of seven T. cruzi antigens in the same model of five new antigens and two well-established candidates. Materials & methods: We evaluated highly immunogenic proteins that contain tandem repeats (FRA [flagelar repetitive protein], Tc3, Tc6); enzymes involved in metabolic pathways critical for parasite survival (cytosolic tryparedoxin peroxidase and tryparedoxin peroxidase); and enzymes involved in parasite invasion (trans-sialidase [TS] and cruzipain)...
June 2017: Immunotherapy
Ian D Davis, Juliet Quirk, Leone Morris, Lauren Seddon, Tsin Yee Tai, Genevieve Whitty, Tina Cavicchiolo, Lisa Ebert, Heather Jackson, Judy Browning, Duncan MacGregor, Frederick Wittke, Gregor Winkels, Regina Alex, Lena Miloradovic, Eugene Maraskovsky, Weisan Chen, Jonathan Cebon
AIM: Pilot clinical trial of NY-ESO-1 (ESO) protein in ISCOMATRIX™ adjuvant pulsed onto peripheral blood dendritic cells (PBDC), to ascertain feasibility, evaluate toxicity and assess induction of ESO-specific immune responses. PATIENTS & METHODS: Eligible participants had resected cancers expressing ESO or LAGE-1 and were at high risk of relapse. PBDC were produced using CliniMACS® plus, with initial depletion of CD1c+ B cells followed by positive selection of CD1c+ PBDC...
March 2017: Immunotherapy
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
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 ISCOMATRIXTM 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...
2016: Current Pharmaceutical Design
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 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
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
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
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
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
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
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
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
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
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
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