Polysaccharide vaccine for staphylococcal infections
AssigneeThe Brigham and Women's Hospital, Inc.
InventorsGerald Pier, Ying Wang, David McKenney
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Abstract
The invention relates to compositions of the capsular polysaccharide/adhesin (PS/A) of staphylococci. The PS/A may be isolated or synthesized and includes various modifications to the structure of native PS/A based on the chemical characterization of PS/A. The invention also relates to the use of the PS/A as a vaccine for inducing active immunity to infections caused by Staphylococcus aureus, S. epidermidis, other related coagulase-negative staphylococci and organisms carrying the ica (intracellular adhesin) locus, and to the use of antibodies directed to PS/A for inducing passive immunity to the same class of infections.
Claims61
A pure PS/A comprising the following structure:
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- wherein n is an integer greater than or equal to 300, wherein R is selected from the group consisting of —NH—CO—(CH2)m—COOH, —NH—CO—CH3, and —NH2, wherein m is 1-5, and wherein at least 50% of the R groups are —NH—CO—CH3 and having a molecular weight of at least 100,000 daltons:
An isolated PS/A, comprising at least 300 monomeric units, at least 50% of which are substituted with acetate, the PS/A having a molecular weight of at least 100,000 Daltons, wherein at least 50% of the units are β-1,6-glucosamine units.
A polysaccharide antigen comprising:
- a PS/A prepared according to the following method:
- preparing an impure PS/A from a bacterial culture,
- incubating the impure PS/A with an acid or a base to produce a semi-pure PS/A preparation;
- neutralizing the preparation, and
- incubating the neutralized preparation in hydrofluoric acid to produce the PS/A.
A PS/A comprising the following structure:
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- wherein n is at least 3, wherein R is selected from the group consisting of —NH—CO—(CH2) m—COOH, —NH—CO—CH3, and —NH2, wherein m is 1-5, provided that at least 50% of the R groups are —NH—CO—CH3, wherein X is either H, a carrier compound, or a linker joined to a carrier compound;
- Y is either OH, a carrier compound or a linker joined to a carrier compound, provided that when X is H, Y is not OH, and wherein when the carrier compound is a polysaccharide it is not an N-acetyl β1-6 glucosamine.
A method of preparing a polysaccharide antigen comprising:
- preparing an impure PS/A from a bacterial culture,
- incubating the impure PS/A with a base or acid to produce a semi-pure PS/A preparation;
- neutralizing the preparation, and
- treating the neutralized preparation to produce the PS/A.
A method for preventing infection by staphylococcus in a subject comprising:
- administering to a non-rodent subject an effective amount for inducing an immune response against staphylococcus of a pure capsular polysaccharide antigen having the following structure:
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- wherein n is at least 3, wherein R is selected from the group consisting of —NH—CO—(CH2) m—COOH, —NH—CO—CH3, and —NH2, wherein m is 1-5, provided that at least 50% of the R groups are —NH—CO—CH3, wherein the subject has not received a medical device implant.
A method for preventing infection by staphylococcus in a subject comprising:
- systemically administering to a non-rodent subject an effective amount for inducing an immune response against staphylococcus of a pure capsular polysaccharide antigen having the following structure:
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- wherein n is at least 3, wherein R is selected from the group consisting of —NH—CO—(CH2) m—COOH, —NH—CO—CH3, and —NH2, wherein m is 1-5, provided that at least 50% of the R groups are —NH—CO—CH3.
Dependencies are inferred from the claim text.