Sanofi Pasteur Sa

Sanofi Pasteur Inc.

Aventis Pasteur S.a.

Biosynth S.r.l.

Noëlle Mistretta

Bachra Rokbi

Monique Moreau

Geneviève Renauld-Mongenie

Philippe Talaga

Massimo Porro

Jean Haensler

Nathalie Guillo

Pierre-Alexandre Driguez

Claude Meric

Olivier Adam

Emilie Danve

Massimo Velucchi

Alessandro Rustici

Tino Krell

François Dalencon

The invention relates to a conjugate of a saccharide covalently bound to a carrier protein, wherein the saccharide comprises repetitive units of 1,5 ribitol phosphate in which all the ribitol residues are substituted by N-acetyl D-glucosaminyl residues at the 4-position, and wherein said N-acetyl D-glucosaminyl residues are exclusively in anomeric configuration &#x3b1; or are exclusively in anomeric configuration &#x3b2; and wherein the carrier protein provides at least one epitope to the conjugate which is recognized by T helper lymphocytes.

Immunogenic compositions against

The invention relates to immunogenic compositions comprising at least two(Nm) protein antigens selected from the group consisting of a trypsin-like serine protease auto-transporter antigen such as IgAI P, App or AusI antigen, a NalP antigen and a TbpB antigen. Preferably, the composition of the invention comprises (i) the trypsin-like serine protease auto-transporter antigen and (ii) the NalP antigen and/or TbpB antigen.

[object Object]

The invention especially relates to multivalent vaccine compositions that can treat or prevent at least 60, preferably 75% of infections caused byespecially of serogroup B. To this end, the invention in particular provides a lipooligosaccharide (LOS) ofin particular constituted by a lipid A, an inner core, an &#x3b1; chain of L6 or L8 type, in which the heptose II residue of the inner core bears in position O-3 and in position O-6 or O-7 a phosphoethanolamine (PEA) substituent, and also to the construction of the strain ofthat is capable of expressing such an LOS. The invention also relates to a strain ofof serogroup A that bears a lipooligosaccharide (LOS) in particular constituted by a lipid A, an inner core, an &#x3b1; chain of L6 type, in which the heptose II residue of the inner core bears in position O-3 a phosphoethanolamine (PEA) substituent and does not bear a PEA substituent in positions O-6 and O-7. The LOSs cited or originating from the mentioned strains may be used as vaccine antigens, especially in multivalent, e.g. divalent compositions, so as to offer protection against the major epiderniological complexes of, especially of serogroup B.

The invention especially relates to multivalent vaccine compositions that can treat or prevent at least 60, preferably 75% of infections caused byespecially of serogroup B. To this end, the invention in particular provides a lipooligosaccharide (LOS) ofin particular constituted by a lipid A, an inner core, an &#x3b1; chain of L6 or L8 type, in which the heptose II residue of the inner core bears in position O-3 and in position O-6 or O-7 a phosphoethanolamine (PEA) substituent, and also to the construction of the strain ofthat is capable of expressing such an LOS. The invention also relates to a strain ofof serogroup A that bears a lipooligosaccharide (LOS) in particular constituted by a lipid A, an inner core, an &#x3b1; chain of L6 type, in which the heptose II residue of the inner core bears in position O-3 a phosphoethanolamine (PEA) substituent and does not bear a PEA substituent in positions O-6 and O-7. The LOSs cited or originating from the mentioned strains may be used as vaccine antigens, especially in multivalent, e.g. divalent compositions, so as to offer protection against the major epidemiological complexes of, especially of serogroup B.

The invention relates to the type 5 and type 8 capsular polysaccharides produced by overproducingstrains, and also to the immunogenic compositions and the vaccines comprising said capsular polysaccharides.

The invention relates to conjugates derived from the reductive amination of the pneumococcus serotypecapsular polysaccharide. The conditions for reductive amination differ from conventional conditions in that they make it possible to avoid the appearance of an undesirable compound which harms the immunogenicity of the conjugates. In carbon NMR spectrum, this undesirable compound is characterized by a resonance signal between 13 and 14 ppm. The aminated polysaccharides used to produce the conjugates therefore have a carbon NMR spectrum lacking a resonance signal between 13 and 14 ppm. The invention offers two conditions for reductive amination. According to a first method, the reductive amination is carried out at a slightly acidic pH (4-6.5) for at the very most 4 hours. According to a second method, the polysaccharide is first of all reduced, then fragmented and, finally, subjected to a reductive amination per se, under conditions which may or may not be conventional. Depending on the method used, the structure of the aminated polysaccharide may vary (conversion or not of the Sug residue of the repeating unit to N-acetylated quinovosamine and to N-acetylated fucosamine); however, these variations, as recorded in carbon NMR spectrometry, have no effect on the immunogenicity.

Conjugates obtained by reductive amination of the pneumococcus serotype 5 capsular polysaccharide

The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS. The dimeric structure is maintained by a pair of disulphide bonds between two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. The peptides in the dimers may have a parallel or anti-parallel orientation. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II diners are non-covalently bound together. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.

Growing community of inventors

Sain Bel, France

Noëlle Mistretta