Claims
- 1. Stable, covalently-coupled polysaccharide-protein conjugates comprising polyanionic bacterial polysaccharides having acid groups and immunogenic proteins coupled through bigeneric spacers, containing thioether bonds, which may be represented by the formula A-E-S-B, wherein E is ##STR35## where R is H or CH.sub.3 ; A is ##STR36## where m is 0 to 4, n is 0 to 3, W is O or NH, and Y is CH.sub.2, O, S, NR', or CHCO.sub.2 H, where R' is H or C.sub.1 - or C.sub.2 -alkyl, such that when Y is CH.sub.2, then both m and n are not equal to zero, and when Y is O or S, then m is 2, 3 or 4 and n is 2 or 3 and B is ##STR37## where p is 1 to 3, q is 0 to 2, Z is NH.sub.2, ##STR38## CO.sub.2 H or H, and D is ##STR39## where R' is as defined above.
- 2. Stable, covalently-coupled polysaccharide-protein conjugates according to claim 1, wherein the bigeneric spacers may be represented by the formula, ##STR40##
- 3. Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is selected from the group consisting of Haemophilus influenzae type b polysaccharide, and Streptococcus pneumoniae types 6B, 19F and 23F polysaccharides.
- 4. Polysaccharide-protein conjugates according to claim 1, wherein the immunogenic protein is a meningococcal B serotype outer membrane protein or edestin protein.
- 5. A stable, covalently-coupled polysaccharide-protein conjugate consisting of an Haemophilus influenzae type b polysaccharide coupled through a spacer of the formula: ##STR41## to a meningococcal B serotype outer membrane protein.
- 6. Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 6B polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR42##
- 7. Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 19F polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR43##
- 8. Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is pneumococcal type 23F polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR44##
- 9. A composition comprising an immunologically-effective amount for either active or passive protection of mammalion species from the bacteremia caused by the cognate organism, of stable, covalently-coupled polysaccharide-protein conjugates according to claim 1, antisera derived from said conjugates, or gamma-globulin or other antibody-containing fractions of said antisera, and a pharmaceutically-acceptable carrier.
- 10. A composition according to claim 9, further comprising an adjuvant.
- 11. A composition according to claim 9 or claim 10, wherein the polysaccharide-protein conjugates comprise one or more members of the group consisting of an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR45## to a meningococcal B serotype outer membrane protein; a pneumococcal type 6B polysaccharide coupled through a bigeneric spacer, of the formula, ##STR46## to a meningococcal B serotype outer membrane protein; a pneumococcal type 19F polysaccharide coupled through a bigeneric spacer of the formula, ##STR47## to a meningococcal B serotype outer membrane protein; and a pneumococcal type 23F polysaccharide coupled through a bigeneric spacer of the formula, ##STR48## to a meningococcal B serotype outer membrane protein.
- 12. A composition according to claim 11, wherein an immunologically-effective amount is an amount of each of the conjugates in the composition such that each conjugate contains from 2-50 .mu.g of the polysaccharide in the conjugate form.
- 13. A composition according to claim 11, wherein the mammalian species is humans.
- 14. A composition according to claim 12, wherein an immunologically-effective amount is an amount of each of the conjugates in the composition such that each conjugate contains 25 .mu.g of the polysaccharide in the conjugate form for conjugates of pneumococcal polysaccharides and 10 .mu.g of the polysaccharide in the conjugate form for conjugates of Haemophilus influenzae type b polysaccharide.
- 15. A method of treating mammalian species against the bacteremia of the cognate organisms, which comprises administering to said species an immunologically-effective amount of a composition comprising one or more types of polysaccharide-protein conjugates comprising bacterial capsular polysaccharides having acid groups coupled through bigeneric spacers, containing thioether bonds, to immunogenic proteins, and a member of the group consisting of a pharmaceutically-acceptable carrier, an adjuvant, and a pharmaceutically-acceptable carrier and adjuvant.
- 16. A method of treating mammalian species according to claim 15, wherein said polysaccharide-protein conjugates comprise one or more members of the group consisting of an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR49## to a meningococcal B serotype outer membrane protein; a pneumococcal type 6B polysaccharide coupled through a bigeneric spacer of the formula, ##STR50## to a meningococcal B serotype outer membrane protein, a pneumococcal type 19F polysaccharide coupled through a bigeneric spacer of the formula, ##STR51## to a meningococcal B serotype outer membrane protein; and a pneumococcal type 23F polysaccharide coupled through a bigeneric spacer of the formula, ##STR52## to a meningococcal B serotype outer membrane protein.
- 17. A method of treating mammalian species according to claim 15, wherein the species to be treated is human infants and children, and the effective amount of the composition in a single dose is an amount corresponding to 25 .mu.g of the polysaccharide in the conjugate form for conjugates of pneumococcal polysaccharides and 10 .mu.g of the polysaccharide in the conjugate form for conjugates of the Haemophilus influenzae type b polysaccharide-protein conjugates being administered.
- 18. A method of treating mammalian species according to claim 17, wherein one or two additional booster compositions of an amount of a polysaccharide-protein conjugate comprising an Haemophilus influenzae type b polysaccharide coupled through a bigeneric spacer of the formula, ##STR53## to a meningococcal B serotype outer membrane protein corresponding to 10 .mu.g of polysaccharide in the conjugate form may be administered to human infants and children.
- 19. Polysaccharide-protein conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is a Group B Streptococcus type Ia, Ib, II or III polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the formula, ##STR54##
- 20. Polysaccharide-prote:n conjugates according to claim 1, wherein the bacterial capsular polysaccharide having acid groups is an Escherichia coli Kl polysaccharide, the immunogenic protein is a meningococcal B serotype outer membrane protein and the bigeneric spacer may be represented by the ##STR55##
Parent Case Info
The present application is a continuation-in-part of U.S. patent application, Ser. No. 608,738, filed May 10, 1984, now abandoned.
US Referenced Citations (8)
Non-Patent Literature Citations (3)
Entry |
Chu et al., Inf. and Immunity, 40 (1), 1983, pp. 245-256. |
S. Marburg et al., J Am Chem Society, 108, 1986, 5282. |
Marburg et al., "Limitation of Cyonogen Bromide Activation of Polysaccharides", Merck Sharp and Dohme Res. Lab. publication. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
608738 |
May 1984 |
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