WO2013178236A1 - Vaccins conjuguant un hydrate de carbone et un glycolipide - Google Patents

Vaccins conjuguant un hydrate de carbone et un glycolipide Download PDF

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Publication number
WO2013178236A1
WO2013178236A1 PCT/EP2012/002277 EP2012002277W WO2013178236A1 WO 2013178236 A1 WO2013178236 A1 WO 2013178236A1 EP 2012002277 W EP2012002277 W EP 2012002277W WO 2013178236 A1 WO2013178236 A1 WO 2013178236A1
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WIPO (PCT)
Prior art keywords
carbohydrate
compound according
antigen
glucopyranose
spp
Prior art date
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Ceased
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PCT/EP2012/002277
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English (en)
Inventor
Peter H. Seeberger
Pierre STALLFORTH
Gennaro DELIBERO
Marco Cavallari
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Universitaetsspital Basel USB
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
Original Assignee
Universitaetsspital Basel USB
Max Planck Gesellschaft zur Foerderung der Wissenschaften eV
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Application filed by Universitaetsspital Basel USB, Max Planck Gesellschaft zur Foerderung der Wissenschaften eV filed Critical Universitaetsspital Basel USB
Priority to PCT/EP2012/002277 priority Critical patent/WO2013178236A1/fr
Priority to HUE13710422A priority patent/HUE028144T2/en
Priority to RU2014142043A priority patent/RU2649009C2/ru
Priority to KR1020147029250A priority patent/KR101675657B1/ko
Priority to JP2015500890A priority patent/JP5933106B2/ja
Priority to DK13710422.0T priority patent/DK2827899T3/en
Priority to HK15106209.7A priority patent/HK1205682A1/xx
Priority to SG11201405646TA priority patent/SG11201405646TA/en
Priority to MX2014011242A priority patent/MX337202B/es
Priority to PCT/EP2013/055719 priority patent/WO2013139803A1/fr
Priority to EP13710422.0A priority patent/EP2827899B1/fr
Priority to PL13710422T priority patent/PL2827899T3/pl
Priority to ES13710422.0T priority patent/ES2551599T3/es
Priority to SI201330079T priority patent/SI2827899T1/sl
Priority to BR112014023193A priority patent/BR112014023193A2/pt
Priority to PT137104220T priority patent/PT2827899E/pt
Priority to TW102109653A priority patent/TWI633112B/zh
Priority to AU2013237497A priority patent/AU2013237497B2/en
Priority to US14/385,948 priority patent/US10588962B2/en
Priority to CN201380015125.5A priority patent/CN104321079A/zh
Priority to CA2866978A priority patent/CA2866978C/fr
Priority to ARP130100898A priority patent/AR090386A1/es
Publication of WO2013178236A1 publication Critical patent/WO2013178236A1/fr
Priority to IL234604A priority patent/IL234604A/en
Anticipated expiration legal-status Critical
Priority to CY20151100848T priority patent/CY1116706T1/el
Priority to JP2016089305A priority patent/JP6235648B2/ja
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
    • A61K39/092—Streptococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Gram-positive bacteria
    • C07K16/1275—Streptococcus (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55572—Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55583—Polysaccharides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines.
  • the new vaccines consist of a multi- modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
  • Adjuvants can be found in a group of structurally heterogeneous compounds (Gupta et al., 1993, Vaccine, 1 1 : 293-306).
  • Classically recognized examples of adjuvants include oil emulsions (e.g., Freund's adjuvant), saponins, aluminium or calcium salts (e.g., alum), non-ionic block polymer surfactants, lipopolysaccharides (LPS), mycobacteria, tetanus toxoid, and many others.
  • oil emulsions e.g., Freund's adjuvant
  • saponins e.g., aluminium or calcium salts (e.g., alum)
  • non-ionic block polymer surfactants e.g., non-ionic block polymer surfactants
  • lipopolysaccharides LPS
  • mycobacteria tetanus toxoid
  • a galactosyiceramide is a glycolipid, more specifically a glycosylceramide, originally isolated from Okinawan marine sponges (Natori et al., Tetrahedron, 50: 2771 -2784, 1994), or its synthetic analog KRN7000 [(2S,3S,4R)-1 -O-(a-D- galactopyranosyl)-2-(N-hexacosanoylamino)-l,3,4-octadecanetriol], which can be obtained from Pharmaceutical Research Laboratories, Kirin Brewery (Gumna, Japan) or synthesized as described previously (see, e.g., Kobayashi et al., 1995, Oncol.
  • ⁇ -GalCer may play an equally important role in bridging not only innate immunity mediated by NKT cells, but also adaptive immunity mediated by B cells, T helper (Th) cells and T cytotoxic (Tc) cells.
  • Th T helper
  • Tc T cytotoxic
  • p is the number of residues -L-CH-CA which are bound to the carbohydrate antigen A, and p is an integer defined as follows
  • p is 1 , 2, 3 or 4 if u is 2
  • p is 1 , 2, 3, 4, 5 or 6 if u is 3
  • x is in integer from 1 to 60;
  • L 2 represents -CH 2 - -C 2 H 4 -, -C 3 H 6 - -C 4 H 8 - -C 5 H 0 - -C 6 H 12 -, -C 7 Hi 4 -, -C8H16-, -C9H18-, -C10H20-, -CH(CH3)-, -C[(CH3)2]-, -CH 2 -CH(CH 3 )-, -CH(CH 3 )-CH 2 - -CH(CH 3 )-C 2 H 4 -, -CH 2 -CH(CH 3 )-CH 2 -, -C 2 H 4 -CH(CH 3 )-, -CH 2 -C[(CH 3 ) 2 ]-, -C[(CH 3 ) 2 ]-CH 2 - -CH(CH 3 )-CH(CH 3 )-, -C[(C 2 H 5 )(CH 3 )]-, -
  • n represents an integer from 1 to 60;
  • CH represents a monosaccharide, a disaccharide or a trisaccharide;
  • CA represents R * and R represent independently of each other a linear or branched or cyclic, substituted or unsubstituted, saturated or unsaturated carbon residue consisting of 1 to 30 carbon atoms; and enantiomers, stereoisomeric forms, mixtures of enantiomers, diastereomers, mixtures of diastereomers, prodrugs, hydrates, solvates, tautomers, and racemates of the above mentioned compounds and pharmaceutically acceptable salts thereof.
  • the term "antigen" can be described as a substance, which is recognized as foreign by the organism of humans and animals and which may cause after introduction into the organism of humans and animals, a specific immune response, which comprises a humoral and/or or a cellular immune response.
  • hydroxylalkyl refers preferably to linear or branched C C 4 hydroxyalkyl residues which consist in total of 1 to 4 carbon atoms including the carbon atoms of the branches wherein one of the hydrogen atoms is substituted by a hydroxyl group such as -CH 2 OH, -C 2 H 4 OH, -CHOHCH3, -CH2CH2CH2OH, -CH2CHOHCH3, -CHOHCH2CH3, -cyclo-C 3 H 4 OH, -COH(CH 3 ) 2 , -CH(CH 3 )CH 2 OH,
  • alkylenyl refers to preferably "linear or branched Ci alkylenyl" such as ⁇
  • the carbohydrate monomers of the A-moiety and the CH moiety are selected independently of each other from the group comprising or consisting of the following a- and ⁇ -D-carbohydrates:
  • L 2 is in case L 3 is not present preferably linked to an oxygen atom of a former hydroxyl group of the carbohydrate residue CH.
  • n represents an integer from 1 to 60;
  • linker moieties L of the moiety A-L-CH-CA as at least one representative of all moieties in the compounds of the general formula (I) as defined herein are
  • the monosaccharide, the disaccharide or the trisaccharide CH is covalently bound by one hydroxyl oxygen atom to L and through another hydroxyl oxygen atom to CA.
  • L or CA is bound to CH, i.e. to the monosaccharide, the disaccharide or the trisaccharide, by a glycosidic bond at C1 of the saccharide.
  • L is bound by a glycosidic bond to C1 of the monosaccharide, the disaccharide or the trisaccharide and CA is bound by the oxygen at C6 of a hexose or by the oxygen at C5 of a pentose or by the oxygen at C4 of a tetrose.
  • glycosidic bonds within CH belong preferably to the group of glycosidic bonds wherein the hydroxyl function of the anomeric carbon is condensed with another hydroxyl fuction of another carbohydrate or of the CA moiety respectively.
  • the glycosidic bond between two carbohydrates comprises the glycosidic bond between the anomeric carbon of one carbohydrate and the non-anomeric carbon of the other carbohydrate. Due to the stereochemistry of the anomeric carbon there is the possibility to form a or ⁇ -glycosidic bonds such as:
  • linear or branched C 2 -C 30 -alkynyl residue refers to a residue which is linked through a carbon atom and which consists in total of 2 to 30 carbon atoms including the carbon atoms of the branches and which has at least one but not more than 15 triple bonds and preferably 1 , 2 or 3 triple bonds. If branched, the longest carbon chain is the main chain while the side chains are the branches. The 1 to 15 C ⁇ C triple bonds may be present in the main chain and/or the side chain(s).
  • substituted C ⁇ Cso-carbon residue containing 1 to 5 of the substituents Z 1 , Z 2 , Z 3 , Z 4 , Z 5 refers to a residue which is linked through a carbon atom and which consists in total of 1 to 30 carbon atoms including the carbon atoms of any substituent such as alkyl, alkenyl, alkinyl, Z Z 2 , Z 3 , Z 4 , and/or Z 5 substituent.
  • the residue bears 1 to 5 of the substituents Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and can be linear or branched and saturated or unsaturated.
  • residues R* and R # represent independently of each other:
  • the residues R* and R are independently of each other substituted with a phenyl ring, preferably an unsubstituted phenyl ring. Further, it is preferred that said phenyl ring is positioned at the residues R * and R at the opposite end where the residues R * and R are bond to the rest of the moiety CA.
  • A, L, R * , R # and p have the meanings as defined herein.
  • A, L, R * , R # and p have the meanings as defined herein.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 represent independently of each other:
  • Another aspect of the present invention comprises the synthesis of the compounds of the general formula (I)
  • the moieties CH and CA are connected via suitable chemical reaction or reactions to yield intermediate CH-CA, and subsequently a linker molecule L is added to yield intermediate L-CH-CA which is then further reacted to furnish the compounds of the present invention of the general formula (I).
  • CH moieties with different connectivity as exemplified in subformulas (II) to (V) may be used.
  • CH moieties being monosaccarides, disaccarides or trisaccarides as exemplified in subformulas (VI) to (XIII), also with respect to stereochemical aspects as exemplified in subformulas (XIV) to (XVII) are suitable for the above reaction sequence.
  • L-CH-CA + A ⁇ A[L— CH— CA] P is suitable also for the synthesis of intermediates (II) to (XXVII) by choosing the respective moieties L, CH, and CA.
  • the bacterial infectious disease for which vaccines can be provided by the compounds according to the invention is caused by a pathogen selected from the group comprising:
  • Powders and tablets may contain about 5 to about 95 weight % of the benzothiophene-1 ,1 -dioxide derived compound and/or the respective pharmaceutically active salt as active ingredient.
  • Suitable binders include starch, gelatin, natural carbohydrates, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes.
  • suitable lubricants there may be mentioned boric acid, sodium benzoate, sodium acetate, sodium chloride, and the like.
  • Suitable disintegrants include starch, methylcellulose, guar gum, and the like. Sweetening and flavoring agents as well as preservatives may also be included, where appropriate. The disintegrants, diluents, lubricants, binders etc. are discussed in more detail below.
  • Liquid form preparations include solutions, suspensions, and emulsions. As an example, there may be mentioned water or water/propylene glycol solutions for parenteral injections or addition of sweeteners and opacifiers for oral solutions, suspensions, and emulsions. Liquid form preparations may also include solutions for intranasal administration. Aerosol preparations suitable for inhalation may include solutions and solids in powder form, which may be present in combination with a pharmaceutically acceptable carrier such as an inert, compressed gas, e.g. nitrogen.
  • a pharmaceutically acceptable carrier such as an inert, compressed gas, e.g. nitrogen.
  • the compounds according to the present invention may also be delivered transdermally.
  • the transdermal compositions may have the form of a cream, a lotion, an aerosol and/or an emulsion and may be included in a transdermal patch of the matrix or reservoir type as is known in the art for this purpose.
  • the amount of binder in the composition may range from about 2 to about 20 weight % of the composition, preferably from about 3 to about 10 weight %, and more preferably from about 3 to about 6 weight %.
  • Lubricants refer to a class of substances which are added to the dosage form to enable the tablet granules etc. after being compressed to release from the mould or die by reducing friction or wear. Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate, or potassium stearate, stearic acid, high melting point waxes, and other water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and D,L- leucine.
  • Another embodiment of the invention comprises the compounds of the invention, according to the general formula (I) which may be used for the preparation of a vaccine formulation for the use in vaccination of an animal.
  • the mentioned vaccine formulation may comprise one or more of the compounds of the present invention or a mixture of different compounds of the invention and preferably of the general formula (I), wherein the mixture of different compounds of the general formula (I) preferably comprises a mixture of different serotypes of the used carbohydrate antigen A, and/or the mixture of different compounds of the general formula (I) may comprise a mixture of different carbohydrate antigens A, which are used in different compounds of the general formula (I).
  • the mentioned mixture of different compounds of the general formula (I) within the vaccine formulation can therefore constitute a combinantion of vaccines which can be used for a combinated vaccination against more than at least one pathogen.
  • the vaccine formulation may comprise a mixture of different compounds of the general formula (I).
  • the compounds of the general formula (I) are present in said vaccine formulation in the range of 10 to 1000 ng/g.
  • mice C57BL/6, BALB/c and B6;129-CD1 ⁇ tm1 Gru> (CD1 KO) [8] mice were bred at our institute (Versuchsstation Departement Biotechnik, Basel, Switzerland) or C57BL/6 were also bought from Charles River Laboratories (Sulzfeld, Germany). This study was reviewed and approved by the "Kantonales Veterinaramt Basel-Stadt" in Basel, Switzerland.
  • glycoconjugate vaccine-induced antibody response is dependent on the presence of iNKT cells and of CD1d as CD1 d KO mice fail to generate high titers of CPS-specific antibodies after immunization.
  • Triol 6 (60 mg, 0.14 mmol) was dissolved in TFA (0.6 mL) and stirred at r.t. for 30 min. The solution was diluted with CH 2 CI 2 (1.5 mL) and then carefully neutralized (to pH ⁇ 8) with sat. aq. NaHC0 3 solution (10 mL) upon which precipitation of a white solid occured. The white solid removed by filtration, washed with water (3 x 10 mL) and dried under reduced pressure. Recrystallization from MeCN yielded phytosphingosine 7 as a white powder (20 mg, 43%).
  • the mode of action is illustrated by the antigen of invasive pneumococcal disease: the pneumococcal capsule polysaccharide (CPS) is covalently attached to a glycolipid.
  • CPS pneumococcal capsule polysaccharide
  • B cells specific for CPS will internalize the conjugate by receptor-mediated endocytosis and the conjugate will be cleaved in late endosomes, generating free aGalCer.
  • aGalCer will be complexed with CD1 d antigen-presenting molecules and upon plasmamembrane recycling of CD1 d be presented to invariant natural killer T (iNKT) cells.
  • FIG. 1 Glycoconjugate vaccine 1 containing the antigenic capsular polysaccharide portion PS4.
  • Figure 3 In vitro activity of the conjugate vaccine.
  • aGalCer-CPS-pulsed CD1 d- positive APC stimulate iNKT cells.
  • Different batches of aGalCer-CPS type 4 conjugate vaccine are active in vitro when aGalCer is freed from CPS in living cells (A).
  • A aGalCer is entirely conjugated to CPS as remaining activity is not found when activating iNKT cells in a cell-free system (B).
  • Unconjugated CPS type 4 open circles
  • aGalCer closed circles alone as control.
  • Figure 4 In vivo activity of the conjugate vaccine. Only aGalCer-CPS increases Abs response in C57BL/6 mice and the Abs response is dependent on NKT cells / CD1 d.
  • A WT C57BL/6 mice vaccinated with aGalCer-CPS (closed symbols) or CPS alone (open symbols) are bled after immunization and the CPS-specific Abs are assessed by ELISA.
  • B WT C57BL/6 (WT, closed symbols) or CD1d-deficient (CD1 d-/-, open symbols) mice immunized with aGalCer-CPS are bled after vaccination and the CPS- specific Abs are measured by ELISA.
  • Figure 5 In vivo antibody response after vaccination.

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Abstract

Cette invention concerne le domaine de la synthèse et de l'évaluation biologique d'une nouvelle classe de vaccins à base d'hydrates de carbone. Les nouveaux vaccins sont constitués d'une structure multi-modulaire où un hydrate de carbone (antigène) est lié par covalence à un glycolipide (adjuvant). Ce procédé permet de préparer des vaccins conférant une protection contre tous les pathogènes exprimant des antigènes hydrates de carbone immunogènes. La conjugaison des antigènes hydrates de carbone à une protéine n'étant pas nécessaire, le vaccin conjugué est particulièrement thermostable. La conservation au froid, inconvénient majeur des vaccins à base de protéines, n'est pas non plus requise.
PCT/EP2012/002277 2012-03-19 2012-05-26 Vaccins conjuguant un hydrate de carbone et un glycolipide Ceased WO2013178236A1 (fr)

Priority Applications (25)

Application Number Priority Date Filing Date Title
PCT/EP2012/002277 WO2013178236A1 (fr) 2012-05-26 2012-05-26 Vaccins conjuguant un hydrate de carbone et un glycolipide
CA2866978A CA2866978C (fr) 2012-03-19 2013-03-19 Vaccins conjugues hydrate de carbone-glycolipide
SI201330079T SI2827899T1 (sl) 2012-03-19 2013-03-19 Konjugirana cepiva s polisaharidinim antigenom in glikolipidom
KR1020147029250A KR101675657B1 (ko) 2012-03-19 2013-03-19 탄수화물-당지질 컨쥬게이트 백신
JP2015500890A JP5933106B2 (ja) 2012-03-19 2013-03-19 炭水化物−糖脂質共役ワクチン
DK13710422.0T DK2827899T3 (en) 2012-03-19 2013-03-19 Polysaccharide-glycolipid conjugate vaccines
HK15106209.7A HK1205682A1 (zh) 2012-03-19 2013-03-19 糖类-糖脂类缀合物疫苗
SG11201405646TA SG11201405646TA (en) 2012-03-19 2013-03-19 Carbohydrate-glycolipid conjugate vaccines
MX2014011242A MX337202B (es) 2012-03-19 2013-03-19 Vacunas de conjugado carbohidrato-glicolipido.
PCT/EP2013/055719 WO2013139803A1 (fr) 2012-03-19 2013-03-19 Vaccins conjugués hydrate de carbone-glycolipide
EP13710422.0A EP2827899B1 (fr) 2012-03-19 2013-03-19 Vaccins conjugués d'antigène polysaccharidique et de glycolipide
PL13710422T PL2827899T3 (pl) 2012-03-19 2013-03-19 Szczepionki zawierające koniugat polisacharydowy antygen-glikolipid
PT137104220T PT2827899E (pt) 2012-03-19 2013-03-19 Vacinas conjugadas de antígeno polissacárido e de glicolipídeo
HUE13710422A HUE028144T2 (en) 2012-03-19 2013-03-19 Polysaccharide antigen-glycolipid conjugate vaccines
BR112014023193A BR112014023193A2 (pt) 2012-03-19 2013-03-19 composto da fórmula geral (i): a[l-ch-ca]p e formulação de vacina
ES13710422.0T ES2551599T3 (es) 2012-03-19 2013-03-19 Vacunas de polisacárido antígeno-glicolípido conjugado
TW102109653A TWI633112B (zh) 2012-03-19 2013-03-19 醣類－醣脂類結合性疫苗
AU2013237497A AU2013237497B2 (en) 2012-03-19 2013-03-19 Carbohydrate-glycolipid conjugate vaccines
US14/385,948 US10588962B2 (en) 2012-03-19 2013-03-19 Carbohydrate-glycolipid conjugate vaccines
CN201380015125.5A CN104321079A (zh) 2012-03-19 2013-03-19 糖类-糖脂类缀合物疫苗
RU2014142043A RU2649009C2 (ru) 2012-03-19 2013-03-19 Углеводно-гликолипидные конъюгированные вакцины
ARP130100898A AR090386A1 (es) 2012-03-19 2013-03-20 Vacunas de conjugado hidrato de carbono-glicolipido
IL234604A IL234604A (en) 2012-03-19 2014-09-11 Carbon-glycophide vaccines are vaccinated
CY20151100848T CY1116706T1 (el) 2012-03-19 2015-09-25 Εμβολια προϊοντος συζευξης αντιγονου πολυσακχαριδιου γλυκολιπιδιου
JP2016089305A JP6235648B2 (ja) 2012-03-19 2016-04-27 炭水化物−糖脂質共役ワクチン

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2012/002277 WO2013178236A1 (fr) 2012-05-26 2012-05-26 Vaccins conjuguant un hydrate de carbone et un glycolipide

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WO2013178236A1 true WO2013178236A1 (fr) 2013-12-05

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PCT/EP2012/002277 Ceased WO2013178236A1 (fr) 2012-03-19 2012-05-26 Vaccins conjuguant un hydrate de carbone et un glycolipide

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3000820A1 (fr) * 2014-09-26 2016-03-30 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Vaccins contre le streptococcus pneumoniae de sérotype 8
WO2016046420A1 (fr) * 2014-09-26 2016-03-31 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Vaccins contre streptococcus pneumoniae sérotype 8
WO2016160429A1 (fr) * 2015-03-23 2016-10-06 Maldonado Rosa Vaccin glycoconjugué contre la leishmaniose
US11246918B2 (en) 2017-02-03 2022-02-15 Eva Barbara Schadeck Haemophilus influenzae saccharide-carrier conjugate compositions and uses thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5936076A (en) 1991-08-29 1999-08-10 Kirin Beer Kabushiki Kaisha αgalactosylceramide derivatives
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WO2016046420A1 (fr) * 2014-09-26 2016-03-31 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Vaccins contre streptococcus pneumoniae sérotype 8
KR20170062458A (ko) * 2014-09-26 2017-06-07 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. 스트렙토코커스 뉴모니에 혈청형 8에 대한 백신
CN106879257A (zh) * 2014-09-26 2017-06-20 马普科技促进协会 针对肺炎链球菌(Streptococcus pneumoniae)血清型8的疫苗
JP2017532321A (ja) * 2014-09-26 2017-11-02 マックス プランク ゲゼルシャフト ツゥアー フェデルゥン デル ヴィッセンシャフテン エー フォー 肺炎連鎖球菌血清型８に対するワクチン
KR102480429B1 (ko) 2014-09-26 2022-12-21 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. 스트렙토코커스 뉴모니에 혈청형 8에 대한 백신
WO2016160429A1 (fr) * 2015-03-23 2016-10-06 Maldonado Rosa Vaccin glycoconjugué contre la leishmaniose
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