Abstract: The present invention provides a method, an assay and a kit for providing an indication of abnormal cell function. It was surprisingly found that the change in the serum ADAM12 concentration in individuals was useful as a prognostic tool to predict the clinical outcome, complications and mortality following an abnormal cell function. The present inventors describes ADAM12 as a overall general marker for abnormal cell function, and the present inventor for the first time demonstrate that ADAM12 is an important indicator of fetal chromosomal disease and placenta function. Specifically ADAM12 is a good marker for e.g. Downs's syndrome, trisomy 18, preeclampsia, Turner syndrome in both first and second trimester. The present inventors developed an enzyme-linked immunosorbent assay (ELISA) and a time-resolved immunofluorometric assay for the quantification of ADAM12 in serum.

Abstract: A convenient way of inducing a broad recognition of dominant and subdominant responses to epitopes of any given antigen of importance for prophylaxis or treatment of a chronic disease is provided. The method involves by immunizing with pools of overlapping fragments (synthetic peptides, e.g., 10-30 mers with 2-20 aa overlap) of the desired antigen in appropriate adjuvants. The T cell repertoire is primed to include not only the immunodominant epitope recognized when the intact molecule is used for immunization and induced by the chronic infection itself, but induce a much broader and balanced response to a number of the subdominant epitopes as well. The vaccination with peptide mix induces a T-cell response that includes response to subdominant epitopes is important for protection against chronic disease that on their own induces a response focused only on immunodominant epitopes.

Abstract: The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M. tuberculosis, M. Bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

Abstract: Vaccination with the combination of Ag85B-TB10.4 and IC31® adjuvant generated a high amount of polyfunctional CD4+T cells expressing high levels of IFN-?, TNF-?, and IL-2. This in turn led to significant protection against infection with M. tuberculosis in the mouse aerosol challenge model of tuberculosis. Both the immunogenicity of the vaccine and its ability to protect against TB infection was highly dependent on the antigen dose. Thus, whereas the standard antigen dose of 5 ?g, as well as 15 ?g, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 ?g increased both the immunogenicity of the vaccine as well as its protective efficacy to a level comparable to that observed in BCG vaccinated mice. Thus, the IC31® adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.

Abstract: The present invention is based on the identification and characterization of a number of novel M. tuberculosis derived proteins and protein fragments. The invention is directed to the polypeptides and immunologically active fragments thereof, the genes encoding them, immunological compositions such as diagnostic reagents containing the polypeptides.

Abstract: The present invention relates to the use of vaccines with adjuvants comprising cationic liposomes where neutral lipids has been incorporated into the liposomes to change the gel-liquid phase transition and thereby modifying the IgG sub-type response and enhancing the CD8 response of the liposomal adjuvant. This technology can be used to increase the production of IgG2 antibodies. This sub-type of anti-bodies (IgG2 in mice corresponding to IgG3 in humans) have been shown to selectively engage Fc activatory receptors on the surface of innate immune cells leading to enhanced proinflammatory responses and thereby a more efficient immune response with higher levels of protection in animal models of e.g. malaria and Chlamydia. The use of adjuvants which selectively give rise to higher levels of IgG2 antibodies will improve the effect of vaccines e.g. against intracellular infections. Furthermore the technology can be used to induce a CD8 response which has been reported to improve the effect of vaccines against e.

Abstract: The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract from Mycobacterium bovis BCG. The total lipid extract contains both apolar lipids, polar lipids, and lipids of intermediate polarity of which the apolar lipids were found to induce the most powerful immune responses. The total lipids may be extracted with chloroform/methanol and re-dissolved in water before the addition of surfactant. This preparation may be used to induce prominent cell-mediated immune responses in a mammal in order to combat pathogens, or as a treatment for cancer.

Abstract: The invention concerns nucleotides vaccines encoding influenza proteins with few or no glycosylation sites. Since these first introductions of pandemic influenzas the viruses have drifted, accumulating mutations at antigenic sites, but also the N-glycosylation pattern has changed during the drifted years, accumulating N-linked glycosylation sequons that help mask the antigenic sites for recognition by the host immune system. These “naked” initial haemagglutinins induce a broad cross reactivity against widely drifted influenza subtypes. The origin of the DNA or RNA can be both pandemic influenza strains, which codes for proteins which have a naturally low content of glycosylation sites and/or DNA or RNA from non-pandemic influenza strains where the nucleotides have been mutated or changed so it encodes for proteins with less or no glycosylation sites. The invention also discloses DNA or RNA encoding the haemagglutinin (HA) from pandemic influenza A, e.g.

Abstract: The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M. tuberculosis, M. Bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

Abstract: The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of the tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, M. microti). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from M. tuberculosis, the units of the fusion polypeptide being M. tuberculosis antigens. Further, the invention is related to the use of a vaccine comprising a fusion polypeptide sequence or nucleic acid sequence of the invention given at the same time as BCG, either mixed with BCG or administered separately at different sites or routes for preparing said immunogenic composition, vaccine, or pharmaceutical composition.

Abstract: A fusion protein, from P. falciparum Glutamate-rich protein (GLURP) genetically coupled to P. falciparum Merozoite surface protein 3 (MSP3) was produced in Lactococcus lactis as a secreted recombinant GLURP-MSP3 hybrid protein and experiments showed that the GLURP-part of the hybrid increased the overall antibody response. Immunizations with the hybrid protein consistently generated a stronger antibody response against the individual GLURP and MSP3 domains than a mixture of the two recombinant molecules injected at one site or the individual recombinant molecules injected simultaneously at two different sites. The difference was most pronounced for the MSP3-specific antibody response suggesting that T cell epitopes located in the GLURP RO-region provide help for B-cell epitopes in the MSP3 region.

Abstract: This invention relates to a polypeptide fragment which comprises an amino acid sequence encoded by a member of the esat-6 gene. A member of the esat-6 gene family is defined as gene encoding a small protein and that two such genes are arranged next to each other on the genome and that at least one of the gene products has an amino acid sequence identity to either Rv3874, Rv3875, or Rv0288 of at least 15%.

Abstract: Dermatophytes which belong to one of the three genera Epidermophyton, Trichophyton and Microsporum are the main cause of fungal infections of skin, hair and nails. Traditional diagnostic procedures consist of microscopy and culture, but due to the slow growth rate of dermatophytes typically two to four weeks are needed before a final diagnosis is obtained. The present invention is a rapid DNA extraction method extracting nucleic acids from fungi (e.g. dermatophytes and other pathogenic fungi) which can be performed from directly on hair, nail or skin specimens from humans, from naturally or experimentally infected animals or from cultured fungal colonies for the use in PCR amplification and detection assays. The present invention also includes specific primer sets for detection of any dermatophyte and for species specific detection of Trichophyton rubrum and Epidermophyton floccosum by PCR and a kit for diagnosing fungal infections.

Abstract: Here we identify MMG and its alpha- and ketomycolic acid derivatives as highly bioactive lipids derived from M. bovis BCG (Copenhagen) capable of stimulating and activating human DC's at exceedingly low doses. In addition to their direct role as immunostimulators of human DC's we demonstrate their use in the development of a new generation of adjuvants suitable for human administration. We furthermore identify a number of highly active synthetic MMG analogues with great potential in cancer treatment, and for vaccine adjuvants against both infectious disease and disorders like Alzheimers disease.

Abstract: The currently used method for immunological diagnosis of tuberculosis infection, the tuberculin skin test, is problematic for a number of reasons; it has low specificity in BCG vaccinated individuals, a high interobserver variance and requires skill to be read and interpreted. Furthermore it requires an extra visit to the clinic to have the test read. Both people vaccinated with BCG and those exposed to non-tuberculosis mycobacteria give a positive skin test result similar to that seen in a TB infected individual. This also applies for purified protein derivative (PPD) when used in a blood cell based test. The present invention discloses the development of an immunological TB diagnostic tool based on a combination of epitopes from proteins encoded by regions of the M. tuberculosis (M. tub.) genome, that are not present in the BCG vaccine strain or in the most common non-tuberculosis mycobacteria.

Abstract: The present invention relates to liposome formulations that are physically stable. In particular the present invention relates to steric stabilization of cationic liposomes by incorporating glycolipids into the liposomes. The stabilized liposomes can be used either as an adjuvant for antigenic components or as a drug delivery system. In particular the invention relates to vaccines with adjuvants in aqueous media for immunization, where the final product is stable.

Abstract: The present nanofiltration method is applicable on solutions of plasma-derived and recombinantly produced MBL. The MBL containing solution is subjected to a pre-treatment prior to the nanofiltration step. The nanofiltration is used for removal of viruses in general and other infectious agents to obtain an MBL product free from infectious viruses and agents. The nanofiltered MBL product is ready for preparing a pharmaceutical composition for therapeutic or prophylactic treatment of infections and other diseases in individuals with MBL deficiency and insufficiency.

Abstract: A fusion protein, derived from P. falciparum Glutamate-rich protein (GLURP) genetically coupled to P. falciparum Merozoite surface protein 3 (MSP3) was produced in Lactococcus lactis as a secreted recombinant GLURP-MSP3 hybrid protein and experiments showed that the GLURP-part of the hybrid increased the overall antibody response. Immunizations with the hybrid protein consistently generated a stronger antibody response against the individual GLURP and MSP3 domains than a mixture of the two recombinant molecules injected at one site or the individual recombinant molecules injected simultaneously at two different sites. The difference was most pronounced for the MSP3-specific antibody response suggesting that T cell epitopes located in the GLURP RO-region provide help for B-cell epitopes in the MSP3 region.

Abstract: The present invention relates to liposome formulations that are physically stable. In particular the present invention relates to steric stabilization of cationic liposomes by incorporating glycolipids into the liposomes. The stabilized liposomes can be used either as an adjuvant for antigenic components or as a drug delivery system. In particular the invention relates to vaccines with adjuvants in aqueous media for immunization, where the final product is stable.

Abstract: Described herein are vaccines and the use of naked DNA and/or RNA encoding hemagglutinin (HA) from pandemic influenza, e.g., the 1918 H1N1 and/or the 1957 H2N2 and/or the 1968 H3N2 influenza A virus, as a vaccine component against present day and coming H1, H2, H3, H5, N1, N2 containing influenza A infections in humans and swine optionally with the naked DNA and/or RNA encoding Neuraminidase (NA) and/or matrix protein (M) and/or the nucleoprotein (NP) from pandemic influenza virus included. If the vaccine components are used as DNA or RNA vaccines with or without the corresponding protein, the codons can optionally be “humanized” using preferred codons from highly expressed mammalian genes and the administration of this DNA vaccine can be by saline or buffered saline injection of naked DNA or RNA, or injection of DNA plasmid or linear gene expressing DNA fragments coupled to particles. Addition of the matrix protein (M) and/or the nucleoprotein (NP) from the 1918 influenza strain is also disclosed.