Uppsala, Sweden
Uppsala, Sweden

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Eliasson D.G.,Gothenburg University | Helgeby A.,Gothenburg University | Schon K.,Gothenburg University | Nygren C.,Gothenburg University | And 6 more authors.
Vaccine | Year: 2011

Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4. °C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation. © 2011 Elsevier Ltd.


Magnusson S.E.,Isconova AB | Reimer J.M.,Isconova AB | Karlsson K.H.,Isconova AB | Lilja L.,Isconova AB | And 3 more authors.
Vaccine | Year: 2013

The novel saponin based adjuvant Matrix-M™ was recently used in a Phase I study of seasonal influenza in elderly. The present study is a pre-clinical evaluation of the efficacy and mode-of-action of Matrix-M™ formulated influenza vaccine in mice. A manuscript on safety profile and immunogenicity in elderly humans is under preparation.We have previously shown that subcutaneous injections of Matrix-M™, without coformulated antigen, results in a dose-dependent recruitment of leukocytes to draining lymph nodes (dLNs). Herein we compared the mode of action of Matrix-M™ with Alum, FCA and AS03 alone or formulated with influenza split virion antigen injected intramuscularly. The elicited responses in dLNs and spleen were investigated 48. h later. Matrix-M™ was particularly efficient in activation of central innate immune cells such as neutrophils, DCs and macrophages compared to the other adjuvants analyzed. Moreover, the adjuvant influence on the recall immune response to influenza antigen was studied by in vitro re-stimulation of splenocytes from mice immunized with influenza antigen adjuvanted with Matrix-M™, Alum or AS03. Splenocytes from mice immunized with influenza antigen and Matrix-M™ produced both Th1 and Th2 cytokines upon re-stimulation. This response was significantly stronger than that induced by the other adjuvants studied. Interestingly, increased levels of the neutrophil chemoattractant KC were produced by antigen stimulated splenocytes from mice immunized with Matrix-M™ adjuvanted vaccine, which is in agreement with the increase of neutrophils into dLNs and spleen after Matrix-M™ injection. Furthermore, influenza antigen adjuvanted with Matrix-M™ induced significantly higher antigen-specific IgG1 and IgG2a responses compared to antigen alone. In conclusion, adjuvant Matrix-M™ activates the innate immune system without antigen present. This activation may explain the enhanced immunity to influenza seen with Matrix-M™ adjuvant. Despite this potent immune activation mediated by Matrix-M™, GLP-toxicity studies and clinical data suggest that Matrix-M™ adjuvant has a mild to moderate safety profile. © 2013 Elsevier Ltd.


Reimer J.M.,Uppsala University | Reimer J.M.,Isconova AB | Samollow P.B.,Texas A&M University | Hellman L.,Uppsala University
Immunogenetics | Year: 2010

Activated mast cells release a number of potent inflammatory mediators including histamine, proteoglycans, cytokines, and serine proteases. The proteases constitute the majority of the mast cell granule proteins, and they belong to either the chymase or the tryptase family. In mammals, these enzymes are encoded by two different loci, the mast cell chymase and the multigene tryptase loci. In mice and humans, a relatively large number of tryptic enzymes are encoded from the latter locus. These enzymes can be grouped into two subfamilies, the group 1 tryptases, with primarily membrane-anchored enzymes, and the group 2 tryptases, consisting of the soluble mast cell tryptases. In order to study the appearance of these enzymes during vertebrate evolution, we have analyzed the dog, cattle, opossum, and platypus genomes and sought orthologues in the genomes of several bird, frog, and fish species as well. Our results show that the overall structure and the number of genes within this locus have been well conserved from marsupial to placental mammals. In addition, two relatively distantly related group 2 tryptase genes and several direct homologues of some of the group 1 genes are present in the genome of the platypus, a monotreme. However, no direct homologues of the individual genes of either group 1 or 2 enzymes were identified in bird, amphibian, or fish genomes. Our results indicate that the individual genes within the multigene tryptase locus, in their present form, are essentially mammal-specific. © 2010 Springer-Verlag.


Andreasson S.,Isconova AB
Expert Review of Vaccines | Year: 2013

Interview by Jenaid Rees, Commissioning Editor Sven Andréasson has held the position of CEO for both pharmaceutical and biotech companies for many years; he was the President and CEO of Active Biotech AB (Sweden) between 1999 and 2008, CEO of Beta-Cell NV (Belgium) until 2012 and currently works as CEO of Isconova AB (Sweden). Prior to this, he held several senior management positions within the international pharmaceutical industry. Andréasson has also held a number of board positions over the years, currently, serving on the boards of Cellastra Inc (CA, USA), Erytech SA (France) and XImmune AB (Sweden). © 2013 Informa UK Ltd.


Ahlberg V.,Swedish University of Agricultural Sciences | Lovgren Bengtsson K.,Isconova AB | Wallgren P.,National Veterinary Institute | Fossum C.,Swedish University of Agricultural Sciences
Developmental and Comparative Immunology | Year: 2012

ISCOM vaccines induce a balanced Th1/Th2 response, long-lasting antibody responses and cytotoxic T lymphocytes. The mode of action for the adjuvant component, the ISCOM-Matrix, is known to some extent but questions remain regarding its mechanism of action. The Affymetrix GeneChip® Porcine Genome Array was applied to study the global transcriptional response to ISCOM-Matrix in pigs at the injection site and in the draining lymph node 24. h after i.m. injection. Gene enrichment analysis revealed inflammation, innate immunity and antigen processing to be central in the ISCOM-Matrix response. At the injection site, 594 genes were differentially expressed, including up-regulation of the cytokines osteopontin (SPP1), IL-10 and IL-18 and the chemokines CCL2, CCL19 and CXCL16. Of the 362 genes differentially expressed in the lymph node, IL-1β and CXCL11 were up-regulated whereas IL18, CCL15 and CXCL12 were down-regulated. ISCOM-Matrix also modulated genes for pattern recognition receptors at the injection site (TLR2, TLR4, MRC1, PTX3, LGALS3) and in the lymph node (TLR4, RIG-I, MDA5, OAS1, EIF2AK2, LGALS3). A high proportion of up-regulated interferon-regulated genes indicated an interferon response. Thus, several genes, genetic pathways and biological processes were identified that are likely to shape the early immune response elicited by ISCOM-based vaccines. © 2012 Elsevier Ltd.


Reimer J.M.,Isconova AB | Karlsson K.H.,Isconova AB | Lovgren-Bengtsson K.,Isconova AB | Magnusson S.E.,Isconova AB | And 3 more authors.
PLoS ONE | Year: 2012

Saponin-based adjuvants are widely used to enhance humoral and cellular immune responses towards vaccine antigens, although it is not yet completely known how they mediate their stimulatory effects. The aim of this study was to elucidate the mechanism of action of adjuvant Matrix-M™ without antigen and Alum was used as reference adjuvant. Adjuvant Matrix-M™ is comprised of 40 nm nanoparticles composed of Quillaja saponins, cholesterol and phospholipid. BALB/c mice were subcutaneously injected once with, 3, 12 or 30 μg of Matrix-M™, resulting in recruitment of leukocytes to draining lymph nodes (dLNs) and spleen 48 h post treatment. Flow cytometry analysis identified CD11b+ Gr-1high granulocytes as the cell population increasing most in dLNs and spleen. Additionally, dendritic cells, F4/80int cells, T-, B- and NK-cells were recruited to dLNs and in spleen the number of F4/80int cells, and to some extent, B cells and dendritic cells, increased. Elevated levels of early activation marker CD69 were detected on T-, B- and NK-cells, CD11b+ Gr-1high cells, F4/80int cells and dendritic cells in dLNs. In spleen CD69 was mainly up-regulated on NK cells. B cells and dendritic cells in dLNs and spleen showed an increased expression of the co-stimulatory molecule CD86 and dendritic cells in dLNs expressed elevated levels of MHC class II. The high-dose (30 μg) of Matrix-M™ induced detectable serum levels of IL-6 and MIP-1β 4 h post administration, most likely representing spillover of locally produced cytokines. A lesser increase of IL-6 in serum after administration of 12 μg Matrix-M™ was also observed. In conclusion, early immunostimulatory properties were demonstrated by Matrix-M™ alone, as therapeutic doses resulted in a local transient immune response with recruitment and activation of central immune cells to dLNs. These effects may play a role in enhancing uptake and presentation of vaccine antigens to elicit a competent immune response. © 2012 Reimer et al.


Patent
Isconova Ab | Date: 2010-07-09

The invention relates to a composition comprising at least one ISCOM complex and at least one internal antigen which is not a surface antigen and not in the form of a part of a whole micro-organism. The internal antigen may be a nucleoprotein or presented as a member of the group of components obtained after disintegrating a micro-organism. The ISCOM complex may be an ISCOM or ISCOM matrix complex. The composition may also comprise non internal antigens. The invention also elates to the composition for use as an immune stimulating medicine or vaccine, especially for use in eliciting T cell respond including CTL respond. The invention also relate to a composition comprising at least one ISCOM complex for use as an immune stimulating or immune modulating medicine or vaccine for the stimulation of dendritic ceils in elderly. Further, the invention relates to a process for preparing a composition wherein a saponin, cholesterol and a lipid are mixed with a lysed cell suspension of cells and solubilising agent without removal of any cell components, where after the solubilising agent is removed or diluted. It also relates to a kit.


Patent
Erasmus University Rotterdam and Isconova Ab | Date: 2011-07-25

The present invention relates to a composition comprising at least one ISCOM complex and at least one ectodomain from at least one hemagglutinin (HA) domain and at least one ectodomain from at least one neuraminidase (NA) domain from one or more influenza virus, wherein the extodomains represent ectodomains isolated from the influenza virus. The invention also regards a kit. The composition may be used as an immune stimulating medicine, immune modulating pharmaceutical or a vaccine e.g. against influenza for vertebrates, e.g. birds and mammals.


Iscom particles can be used as an adjuvant for preparing of an antigenic composition which comprises live micro-organisms and/or killed micro-organisms and/or antigenic molecules. A composition may comprise at least one iscom particle and one or more live micro-organisms and/or killed micro-organisms and/or antigenic molecules. A kit can comprise at least one compartment containing at least one living organism and at least one compartment containing at least one iscom particle.


The present invention relates to a composition comprising at least one fibronectin binding protein, and/or at least one a truncated fibronectin binding protein and/or at least one fibronectin binding peptide, all comprising at least one fibronectin binding domain; and at least one iscom matrix complex and/or liposome and/or at least one lipid and at least one saponin, whereby the at least one lipid and the at least one saponin may be in complex, solution or suspension. Further, it regards use thereof for the preparation of a vaccine against a micro organism that comprises at least one fibronectin binding domain. It also relates to a kit of parts comprising at least two compartments, wherein one compartment comprises at least one truncated fibronectin binding protein and/or a fibronectin binding peptide, that comprises at least one fibronectin binding domain, and another compartment comprises an instruction for use and/or an iscom matrix complex and/or an iscom complex and or a liposome. Further it relates to a method for vaccination of an individual.

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