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. 1996 Nov 15;98(10):2308–2314. doi: 10.1172/JCI119042

Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine.

D L Kasper 1, L C Paoletti 1, M R Wessels 1, H K Guttormsen 1, V J Carey 1, H J Jennings 1, C J Baker 1
PMCID: PMC507681  PMID: 8941648

Abstract

Group B Streptococcus (GBS) is an important perinatal pathogen. Because transplacentally acquired maternal antibodies to the GBS capsular polysaccharides (CPS) confer protection, prevention of infant disease may be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enhance immunogenicity we have designed and developed a CPS-protein conjugate vaccine. The lability of a conformationally dependent epitope on the III CPS containing a critical sialic acid residue was important to consider in vaccine design. 100 women were randomized to receive GBS type III CPS-tetanus toxoid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline. Serum samples were obtained before immunization and 2, 4, 8, and 26 wk thereafter, and specific antibody to type III CPS was measured. Vaccines were well tolerated. In sera from recipients of the highest dose of III-TT, CPS-specific IgG levels rose from a geometric mean of 0.09 microg/ml before immunization to 4.53 microg/ml 8 wk later, whereas levels in recipients of unconjugated type III CPS rose from 0.21 microg/ml to 1.41 microg/ml. Lower doses resulted in lower antibody levels. A > or = 4-fold rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015). Antibodies evoked by the conjugate vaccine recognized a conformationally dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal mice from lethal challenge with type III GBS. We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile conformational epitope involving sialic acid and enhanced immunogenicity compared with uncoupled CPS.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baker C. J., Edwards M. S., Kasper D. L. Role of antibody to native type III polysaccharide of group B Streptococcus in infant infection. Pediatrics. 1981 Oct;68(4):544–549. [PubMed] [Google Scholar]
  2. Baker C. J., Kasper D. L. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med. 1976 Apr 1;294(14):753–756. doi: 10.1056/NEJM197604012941404. [DOI] [PubMed] [Google Scholar]
  3. Baker C. J., Kasper D. L. Group B streptococcal vaccines. Rev Infect Dis. 1985 Jul-Aug;7(4):458–467. doi: 10.1093/clinids/7.4.458. [DOI] [PubMed] [Google Scholar]
  4. Baker C. J., Kasper D. L., Tager IRAB, Paredes A., Alpert S., McCormack W. M., Goroff D. Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B Streptococcus. J Clin Invest. 1977 May;59(5):810–818. doi: 10.1172/JCI108703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baker C. J., Rench M. A., Edwards M. S., Carpenter R. J., Hays B. M., Kasper D. L. Immunization of pregnant women with a polysaccharide vaccine of group B streptococcus. N Engl J Med. 1988 Nov 3;319(18):1180–1185. doi: 10.1056/NEJM198811033191802. [DOI] [PubMed] [Google Scholar]
  6. Englund J. A., Glezen W. P., Turner C., Harvey J., Thompson C., Siber G. R. Transplacental antibody transfer following maternal immunization with polysaccharide and conjugate Haemophilus influenzae type b vaccines. J Infect Dis. 1995 Jan;171(1):99–105. doi: 10.1093/infdis/171.1.99. [DOI] [PubMed] [Google Scholar]
  7. Farley M. M., Harvey R. C., Stull T., Smith J. D., Schuchat A., Wenger J. D., Stephens D. S. A population-based assessment of invasive disease due to group B Streptococcus in nonpregnant adults. N Engl J Med. 1993 Jun 24;328(25):1807–1811. doi: 10.1056/NEJM199306243282503. [DOI] [PubMed] [Google Scholar]
  8. Guttormsen H. K., Baker C. J., Edwards M. S., Paoletti L. C., Kasper D. L. Quantitative determination of antibodies to type III group B streptococcal polysaccharide. J Infect Dis. 1996 Jan;173(1):142–150. doi: 10.1093/infdis/173.1.142. [DOI] [PubMed] [Google Scholar]
  9. Harrison L. H., Ali A., Dwyer D. M., Libonati J. P., Reeves M. W., Elliott J. A., Billmann L., Lashkerwala T., Johnson J. A. Relapsing invasive group B streptococcal infection in adults. Ann Intern Med. 1995 Sep 15;123(6):421–427. doi: 10.7326/0003-4819-123-6-199509150-00004. [DOI] [PubMed] [Google Scholar]
  10. Hornick C. L., Karuch F. Antibody affinity. 3. The role of multivalance. Immunochemistry. 1972 Mar;9(3):325–340. doi: 10.1016/0019-2791(72)90096-1. [DOI] [PubMed] [Google Scholar]
  11. Häyrinen J., Pelkonen S., Finne J. Structural similarity of the type-specific group B streptococcal polysaccharides and the carbohydrate units of tissue glycoproteins: evaluation of possible cross-reactivity. Vaccine. 1989 Jun;7(3):217–224. doi: 10.1016/0264-410x(89)90232-6. [DOI] [PubMed] [Google Scholar]
  12. Jackson L. A., Hilsdon R., Farley M. M., Harrison L. H., Reingold A. L., Plikaytis B. D., Wenger J. D., Schuchat A. Risk factors for group B streptococcal disease in adults. Ann Intern Med. 1995 Sep 15;123(6):415–420. doi: 10.7326/0003-4819-123-6-199509150-00003. [DOI] [PubMed] [Google Scholar]
  13. Jennings H. J., Lugowski C., Kasper D. L. Conformational aspects critical to the immunospecificity of the type III group B streptococcal polysaccharide. Biochemistry. 1981 Aug 4;20(16):4511–4518. doi: 10.1021/bi00519a001. [DOI] [PubMed] [Google Scholar]
  14. Lancefield R. C., McCarty M., Everly W. N. Multiple mouse-protective antibodies directed against group B streptococci. Special reference to antibodies effective against protein antigens. J Exp Med. 1975 Jul 1;142(1):165–179. doi: 10.1084/jem.142.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mohle-Boetani J. C., Schuchat A., Plikaytis B. D., Smith J. D., Broome C. V. Comparison of prevention strategies for neonatal group B streptococcal infection. A population-based economic analysis. JAMA. 1993 Sep 22;270(12):1442–1448. [PubMed] [Google Scholar]
  16. Paoletti L. C., Kasper D. L., Michon F., DiFabio J., Jennings H. J., Tosteson T. D., Wessels M. R. Effects of chain length on the immunogenicity in rabbits of group B Streptococcus type III oligosaccharide-tetanus toxoid conjugates. J Clin Invest. 1992 Jan;89(1):203–209. doi: 10.1172/JCI115564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Paoletti L. C., Wessels M. R., Michon F., DiFabio J., Jennings H. J., Kasper D. L. Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1992 Oct;60(10):4009–4014. doi: 10.1128/iai.60.10.4009-4014.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reed G. F., Meade B. D., Steinhoff M. C. The reverse cumulative distribution plot: a graphic method for exploratory analysis of antibody data. Pediatrics. 1995 Sep;96(3 Pt 2):600–603. [PubMed] [Google Scholar]
  19. Rodewald A. K., Onderdonk A. B., Warren H. B., Kasper D. L. Neonatal mouse model of group B streptococcal infection. J Infect Dis. 1992 Sep;166(3):635–639. doi: 10.1093/infdis/166.3.635. [DOI] [PubMed] [Google Scholar]
  20. Schuchat A., Deaver-Robinson K., Plikaytis B. D., Zangwill K. M., Mohle-Boetani J., Wenger J. D. Multistate case-control study of maternal risk factors for neonatal group B streptococcal disease. The Active Surveillance Study Group. Pediatr Infect Dis J. 1994 Jul;13(7):623–629. doi: 10.1097/00006454-199407000-00008. [DOI] [PubMed] [Google Scholar]
  21. Schuchat A., Wenger J. D. Epidemiology of group B streptococcal disease. Risk factors, prevention strategies, and vaccine development. Epidemiol Rev. 1994;16(2):374–402. doi: 10.1093/oxfordjournals.epirev.a036159. [DOI] [PubMed] [Google Scholar]
  22. Wessels M. R., Kasper D. L. Antibody recognition of the type 14 pneumococcal capsule. Evidence for a conformational epitope in a neutral polysaccharide. J Exp Med. 1989 Jun 1;169(6):2121–2131. doi: 10.1084/jem.169.6.2121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wessels M. R., Muñoz A., Kasper D. L. A model of high-affinity antibody binding to type III group B Streptococcus capsular polysaccharide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9170–9174. doi: 10.1073/pnas.84.24.9170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wessels M. R., Paoletti L. C., Kasper D. L., DiFabio J. L., Michon F., Holme K., Jennings H. J. Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus. J Clin Invest. 1990 Nov;86(5):1428–1433. doi: 10.1172/JCI114858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wessels M. R., Paoletti L. C., Pinel J., Kasper D. L. Immunogenicity and protective activity in animals of a type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J Infect Dis. 1995 Apr;171(4):879–884. doi: 10.1093/infdis/171.4.879. [DOI] [PubMed] [Google Scholar]
  26. Wessels M. R., Paoletti L. C., Rodewald A. K., Michon F., DiFabio J., Jennings H. J., Kasper D. L. Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1993 Nov;61(11):4760–4766. doi: 10.1128/iai.61.11.4760-4766.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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