Sanofi Pasteur Sa

Aventis Pasteur S.a.

Pasteur Merieux Serums Et Vaccines

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

Sanofi Pasteur Inc.

Biosynth S.r.l.

Pasteur Merieux Serums, Et Vaccins S.a.

Mark Achtman

Monique Moreau

Noëlle Mistretta

Bachra Rokbi

Massimo Porro

Jean Haensler

Geneviève Renauld-Mongenie

Alessandro Rustici

Tino Krell

No&euml;lle Mistretta

Emilie Danve

Massimo Velucchi

François Dalencon

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.

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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 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.

Polymyxin B analogs for LPS detoxification

The present invention is concerned with a fragment of IgA1-protease having 40 to 200 amino acid residues and comprising at least 40 amino acids of an amino acid sequence as shown in SEQ ID NO:1, beginning with the amino acid in any one of positions 1 to 5 and ending with an amino acid in any one of positions 40 to 104 or a homologous sequence, its use as a carrier for a conjugate, particularly in combination with a polysaccharide, and a process for producing the peptide as well as vaccines comprising said peptide.

IgA1 protease fragment as carrier peptides

The invention relates to a method for reductive amination of polysaccharides which comprises subjecting a reaction mixture comprising a polysaccharide, an amino compound and a reducing agent, to microwave radiation for a period of time sufficient to aminate the polysaccharide.

Method for the reductive amination of polysaccharides

The invention relates to a polysaccharide-peptide conjugate wherein the polysaccharide is advantageously immunogenic, which comprises a polysaccharide chain composed of repeat units and a plurality of peptide moieties, each moiety containing a cysteine residue and being covalently attached at random along the polysaccharide chain, through an indirect bond being achieved through either a linker or a spacer-linker moiety provided that the spacer entity of the spacer-linker moiety is linked to the amino, hydroxyl or carboxyl group of the polysaccharide. To this end a useful linker may be, e.g., N-(&ggr;-maleimidobutyrloxy)succinimide ester. Such a conjugate may typically exhibit a &ldquo;Rake&rdquo; configuration. Conjugation processes are also disclosed. Conjugates of the invention are in particular useful in the vaccinal field to elicit a protective long term immune response against a pathogenic microorganism from which the Immunogenic polysaccharide is derived.

Polysaccharide-peptide-conjugates

An oligosaccharide derived from an antigen polysaccharide obtained from a pathogenic agent, a method for its preparation, and its use particularly as a vaccinal agent. The oligosaccharide is prepared by oxidation-reduction depolymerization reaction.

Oligosaccharide derived from an antigenic polysaccharide obtained from a

An oligoside derived from an antigen polyoside obtained from a pathogenic agent, a method for its preparation, and its use particularly as a vaccinal agent. The oligoside is prepared by oxidation-reduction depolymerisation reaction.

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Lyons, France

Monique Moreau