Glaxosmithkline Biologicals Sa

Novartis Ag

Novartis Vaccines and Diagnostics Srl

J. Craig Venter Institute

Chiron S.r.l.

Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

Institut Pasteur

Biocine S.p.a.

Novartis Ac

Chrion S.r.l.

J. Craig Venture Institute, Inc.

Statens Institutt for Folkehelse

Glaxosmithkline Vaccines S.r.l.

Luciano Nencioni

Mariagrazia Pizza

Rino Rappuoli

Vega Masignani

Maria Scarselli

Guido Grandi

Marzia Monica Giuliani

Cesira Galeotti

Vincenzo Scarlato

Herve Tettelin

Claire M Fraser

Maurizio Comanducci

Maria Rita Fontana

Marirosa Mora

Laura Serino

Erin Hickey

Giulio Ratti

Jeremy Petersen

J Craig Venter

Nathalie Norais

Danilo Gomes Moriel

Maria Arico

Francesco Berlanda Scorza

Davide Serruto

Antonella Bartoloni

Maria Aricò

Jeannette Adu-Bobie

Guilio Ratti

Germano Ferrari

Elisabetta Monaci

Mario Contorni

Antonello Covacci

Manuele Martinelli

Isabel Delany

Brunella Brunelli

Silvana Savino

Mariarosa Mora

Marizia Monica Guiliani

Hervé Tettelin

Valentina Giannelli

Rosanna Leuzzi

Muhamed-Kheir Taha

Johan Holst

Craig Venter

Maria Beatrice Arico

Daniele Veggi

Gillian Douce

Ala-Eddine Deghmane

Philipp Oster

Rino Rappouli

Marzia Monica Guiliani

Beatrice Maria Arico

Maria Rosa Mora

Giulo Ratti

Jeremy D Peterson

Craig Ventor

Vega Masiganani

Peter Dull

Mario Domenighini

Meera Unnikrishnan

Wim Hol

Eva Hong

Anja Seubert

Steven B Black

Isobel Delany

Marzia Giuliani

Mazia Monica Giuliani

Laura Ciucchi

Federica Di Marcello

Maria B Arico

Methods and compositions for immunizing a human subject against

Vaccines for

The invention provides an immunogenic composition comprising OMVs and (a) acellular pertussis antigen, (b) a tetanus toxoid and (c) a diphtheria toxoid, wherein the OMVs are derived from. The invention also provides compositions for use in a method for raising an immune response in a patient, comprising the step of administering to the patient a composition of the invention.

Immunogenic compositions comprising OMVs, an acellular pertussis antigen, a tetanus toxoid and a diphtheria toxoid

A method for immunizing a subject in need thereof againstby administering an immunogenic composition comprising meningococcal outer membrane vesicles (OMVs).

The M01573 sequence of meningococcal fHbp offers poor coverage in a vaccine. The invention addresses this poor coverage in two ways. In a first aspect, a fHbp-based vaccine includes two family I fHbp sequences, one which is more closely related to MC58 than to M01573, and vice versa. In a second aspect, a multi-family fHbp-based vaccine uses a family I fHbp sequence which is more closely related to MC58 than to M01573, in combination with a family III fHbp sequence. The compositions are adjuvanted with an aluminium phosphate adjuvant.

Adjuvanted combinations of meningococcal factor H binding proteins

The M01573 sequence of meningococcal fHbp offers poor coverage in a vaccine. The invention addresses this poor coverage in two ways. In a first aspect, a fHbp-based vaccine includes two family I fHbp sequences, one which is more closely related to MC58 than to M01573, and vice versa. In a second aspect, a multi-family fHbp-based vaccine uses a family I fHbp sequence which is more closely related to MC58 than to M01573, in combination with a family III fHbp sequence.

Combinations of meningococcal factor H binding proteins

A method for immunizing a subject against serogroup X meningococcus by administering a vaccine comprising one, two or all three of: (i) a meningococcal fHbp antigen; (ii) a meningococcal NHBA antigen; and/or (iii) a meningococcal NadA antigen. The vaccine may also include meningococcal outer membrane vesicles.

Vaccines for serogroup X meningococcus

Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titres than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.

Immunogenic bacterial vesicles with outer membrane proteins

Meningococcal protein NMB 1870 has been described in the prior art. The inventors have found that NMB 1870 is an effective antigen for eliciting anti-meningococcal antibody responses, and that it is expressed across all meningococcal serogroups. Forty-two different NMB 1870 sequences have been identified, and these group into three variants. Serum raised against a given variant is bactericidal within the same variant group, but is not active against strains which express one of the other two variants i.e. there is intra-variant cross-protection, but not inter-variant cross-protection. For maximum cross-strain efficacy, therefore, the invention uses mixture comprising different variants of NMB 1870.

Multiple variants of meningococcal protein NMB1870

The invention uses polypeptide antigens and/or OMVs to immunize against serogroups A, C, W135 and Y (and against serogroup Y in particular). Serogroup B polypeptides can achieve this protection, thus permitting a single polypeptide-based vaccine to be used for protecting against all of serogroups A, B, C, W135 and Y.

Immunising against meningococcal serogroup Y using proteins

A first aspect of the invention provides meningococcal outer membrane vesicles in which NHBA is over-expressed. A second aspect of the invention provides meningococcal outer membrane vesicles in which NadA is over-expressed. A third aspect of the invention provides a panel of bacterial strains, each member of which is isogenic except for a single gene which in each strain encodes a different variant antigen of interest.

Developments in meningococcal outer membrane vesicles

The invention provides an immunogenic composition comprising a combination of (i) bacterial Ig-like domain protein fragment (orf405B) having the amino acid sequence set forth in SEQ ID NO:2 or a protein having at least 80% similarity thereto, and (ii) putative Lipoprotein (orf3526) having the amino acid sequence set forth in SEQ ID NO:8 or a protein having at least 80% similarity thereto.

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Disclosed herein are various open reading frames from a strain ofresponsible for neonatal meningitis (MNEC), and a subset of these that is of particular interest for preparing compositions for immunizing against MNEC infections.

The invention provides methods, proteins, nucleic acids and antibodies for preventing or treating ainfection in a mammal.

Clostridium difficile polypeptides as vaccine

Knockout of the meningococcal mltA homolog gives bacteria that spontaneously release vesicles that are rich in immunogenic outer membrane proteins and that can elicit cross-protective antibody responses with higher bactericidal titers than OMVs prepared by normal production processes. Thus the invention provides a bacterium having a knockout mutation of its mltA gene. The invention also provides a bacterium, wherein the bacterium: (i) has a cell wall that includes peptidoglycan; and (ii) does not express a protein having the lytic transglycosylase activity MltA protein. The invention also provides compositions comprising vesicles that, during culture of bacteria of the invention, are released into the culture medium.

The present invention relates to recombinant fragments ofTcdA and TcdB that may be used in the development of vaccines againstassociated disease. More particularly it relates to combinations comprising a ToxB-GT antigen and a TcdA antigen or a ToxA-GT antigen and a TcdB antigen.

Clostridium difficile toxin-based vaccine

Growing community of inventors

Siena, Italy

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