Statens Serum Institut

Institut Pasteur

Serum Statens Institut

Peter Andersen

Claus Aagaard

Ida Rosenkrands

Peter Birk Rasmussen

Jes Dietrich

Anja Olsen

Karin Weldingh

Carina Vingsbo-Lundberg

Walter Florio

Rikke Louise Vinther Skjot

Else Marie Agger

Erik B Lindblad

Jesper Davidsen

Frank Follmann

Truc Thi Kim Thanh Hoang

Christina Veggerby Hansen

Li Mei Meng Okkels

Martin J Elhay

Lise Ostergaard Brandt

Truc Thi Kim Than Hoang

Carina Vingsbo Lundberg

Rikke Louise Vinther Skjøt

Brigitte Gicquel

Klaus Gjervig Jensen

Gurdyal S Besra

Michael Theisen

Francois-Xavier Berthet

ANGse Bengaard Andersen

Thomas Oettinger

David E Minnikin

Rikke Nielsen

Anne Lund Sorensen

Kaare Haslov

Anette Stryhn

Robert Leah

Inger Brock

Claire Andersen

Claus Aagard

Gurdyal Bersra

David Minikin

The present invention describes an efficient vaccine against a(Ct). The vaccine is based on recombinant fusion molecules that are capable of generating a high titered neutralizing antibody response that is protective against various Ct serovars. Our invention furthermore describe the combination of these antibody promoting fragments with Ct antigens that are targets for T cells with the aim to provide a vaccine that activate both arms of the immune system.

Vaccines againstsp

The present invention discloses a vaccine or immunogenic composition that can be administered to latently infected individuals to prevent reactivation of latent tuberculosis infection caused by species of the tuberculosis complex microorganisms (), The invention is based on a number ofderived proteins and protein fragments which are constitutively expressed in different stages of the infection. The invention is directed to the use of these polypeptides, immunologically active fragments thereof and the genes encoding them for immunological compositions such as vaccines.

Tuberculosis TB vaccine to prevent reactivation

The present invention is directed to a fusion protein, antigen cocktails and immunological compositions such as vaccines against infections caused by virulent mycobacteria, e.g. byor. The fusion protein, antigen cocktails and immunological compositions are based on proteins secreted by the ESAT-6 secretion system 1 (ESX-1) and are among the most immunodominant(MTB) antigens.

M.tuberculosis vaccines

Vaccination with the combination of Ag85B-TB10.4 and IC31&#xae; adjuvant generated a high amount of polyfunctional CD4T cells expressing high levels of IFN-&#x3b3;, TNF-&#x3b1;, 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 &#x3bc;g, as well as 15 &#x3bc;g, did not induce significant protection against M. tuberculosis, reducing the dose to 0.5 &#x3bc;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&#xae; adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against M. tuberculosis.

Vaccines comprising TB10.4

The present invention is directed to fusion proteins, antigen cocktails and immunological compositions such as vaccines against infections caused by virulent mycobacteria, e.g. byor. The fusion proteins or antigen cocktails are based on ESX secreted or associated proteins e.g. proteins secreted by the ESAT-6 secretion system 1 (ESX-1) which are among the most immunodominant(MTB) antigens.

[object Object]

The present invention discloses a vaccine or immunogenic composition that can be administered to latently infected individuals to prevent reactivation of latent tuberculosis infection caused by species of the tuberculosis complex microorganisms (). The invention is base on a number ofderived proteins and protein fragments which are constitutively expressed in different stages of the infection. The invention is directed to the use of these polypeptides, immunologically active fragments thereof and the genes encoding them for immunological compositions such as vaccines.

The present invention is related to antigen fromwhich are recognized by specific antibodies from individuals infected withor which can induce T cells from the same individuals to secrete gamma-interferon. The T cell reactive antigens are present in a whole-cell lysate and have apparent molecular weights of 5-12, 16-20, 25-35 and 58-74 kDa as determined by SDS-PAGE. The antigens of the invention are believed to be useful in vaccines but also as diagnostic compositions.

Here we identify MMG and its alpha- and ketomycolic acid derivatives as highly bioactive lipids derived fromBCG (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.

Use of monomycolyl glycerol (MMG) as an adjuvant

Vaccination with the combination of Ag85B-TB10.4 and IC31&#xae; adjuvant generated a high amount of polyfunctional CD4T cells expressing high levels of IFN-&#x3b3;, TNF-&#x3b1;, and IL-2. This in turn led to significant protection against infection within 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 &#x3bc;g, as well as 15 &#x3bc;g, did not induce significant protection against, reducing the dose to 0.5 &#x3bc;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&#xae; adjuvant, with the specified antigen dose, can induce a strong protective Th1 response against

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 (). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from, the units of the fusion polypeptide beingantigens. 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.

Tuberculosis vaccines comprising antigens expressed during the latent infection phase

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.

Compositions and methods for stabilizing lipid based adjuvant formulations using glycolipids

The present invention provides a vaccine adjuvant consisting of a combination of a surfactant i.e. dimethyldeoctadecylammonium-bromide/chloride (DDA) and a lipid extract fromBCG. 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.

Adjuvant combinations of liposomes and mycobacterial lipids for immunization compositions and vaccines

Therapeutic vaccines comprising polypeptides expressed during the latent stage of mycobacteria infection are provided, as are multiphase vaccines, and methods for treating and preventing

Therapeutic TB vaccine

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. The major advantage of the present invention is that it requires no prior knowledge of the precise localization and identity of the subdominant epitopes and their recognition in a human population, but expands the T-cell repertoire and thereby the total number of epitopes recognized by specific T cells primed by vaccination from a few immunodominant epitopes to a multiple of epitopes.

Expanding the T cell repertoire to include subdominant epitopes by vaccination with antigens delivered as protein fragments or peptide cocktails

The invention is related to an immunogenic composition, vaccine or pharmaceutical composition for preventing, boosting or treating infection caused by a species of thecomplex (). The immunogenic composition, vaccine or pharmaceutical composition comprise a fusion polypeptide, which comprises one or more starvation antigens from, the units of the fusion polypeptide beingantigens. 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.

Growing community of inventors

Brønshøj, Denmark

Peter Andersen