Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1996 Sep;64(9):3518–3523. doi: 10.1128/iai.64.9.3518-3523.1996

Experimental vaccination against group B streptococcus, an encapsulated bacterium, with highly purified preparations of cell surface proteins Rib and alpha.

C Larsson 1, M Stålhammar-Carlemalm 1, G Lindahl 1
PMCID: PMC174257  PMID: 8751893

Abstract

Encapsulated bacteria cause some of the most common diseases in humans. Although the polysaccharide capsules of these pathogens have attracted the most attention with regard to vaccine development, recent evidence suggests that bacterial surface proteins may also be used to confer protective immunity. We have analyzed this possibility in group B streptococcus (GBS), an encapsulated bacterium that is the major cause of invasive bacterial disease in the neonatal period. Previous work has shown that the majority of GBS strains causing invasive infections express the Rib protein, and that most strains lacking Rib express a protein designated alpha. Here we report that active immunization with highly purified preparations of Rib or alpha protected mice against lethal infection with strains expressing the corresponding protein. Vaccination with the Rib protein protected against two strains of capsular type III and two strains of type II, and vaccination with the alpha protein protected against one strain of type II and one strain of type Ib. The mice vaccinated with Rib or alpha showed a good immunoglobulin G response to the immunogen. These data suggest that a vaccine against GBS disease may be based on cell surface proteins and support the notion that proteins may be used for immunization against encapsulated bacteria.

Full Text

The Full Text of this article is available as a PDF (429.9 KB).

Selected References

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

  1. Ala'Aldeen D. A., Stevenson P., Griffiths E., Gorringe A. R., Irons L. I., Robinson A., Hyde S., Borriello S. P. Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design. Infect Immun. 1994 Jul;62(7):2984–2990. doi: 10.1128/iai.62.7.2984-2990.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander J. E., Lock R. A., Peeters C. C., Poolman J. T., Andrew P. W., Mitchell T. J., Hansman D., Paton J. C. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect Immun. 1994 Dec;62(12):5683–5688. doi: 10.1128/iai.62.12.5683-5688.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Austrian R. Pneumococcal polysaccharide vaccines. Rev Infect Dis. 1989 May-Jun;11 (Suppl 3):S598–S602. doi: 10.1093/clinids/11.supplement_3.s598. [DOI] [PubMed] [Google Scholar]
  4. Baker C. J. Vaccine prevention of group B streptococcal disease. Pediatr Ann. 1993 Dec;22(12):711–714. doi: 10.3928/0090-4481-19931201-05. [DOI] [PubMed] [Google Scholar]
  5. Bevanger L. Ibc proteins as serotype markers of group B streptococci. Acta Pathol Microbiol Immunol Scand B. 1983 Aug;91(4):231–234. doi: 10.1111/j.1699-0463.1983.tb00038.x. [DOI] [PubMed] [Google Scholar]
  6. Bevanger L., Naess A. I. Mouse-protective antibodies against the Ibc proteins of group B streptococci. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):121–124. doi: 10.1111/j.1699-0463.1985.tb02862.x. [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. Finne J., Leinonen M., Mäkelä P. H. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet. 1983 Aug 13;2(8346):355–357. doi: 10.1016/s0140-6736(83)90340-9. [DOI] [PubMed] [Google Scholar]
  9. Frasch C. E. Vaccines for prevention of meningococcal disease. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S134–S138. doi: 10.1128/cmr.2.suppl.s134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hedén L. O., Frithz E., Lindahl G. Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline-rich region with unique structure and isolation of N-terminal fragments with IgA-binding capacity. Eur J Immunol. 1991 Jun;21(6):1481–1490. doi: 10.1002/eji.1830210623. [DOI] [PubMed] [Google Scholar]
  11. Jerlström P. G., Chhatwal G. S., Timmis K. N. The IgA-binding beta antigen of the c protein complex of Group B streptococci: sequence determination of its gene and detection of two binding regions. Mol Microbiol. 1991 Apr;5(4):843–849. doi: 10.1111/j.1365-2958.1991.tb00757.x. [DOI] [PubMed] [Google Scholar]
  12. Jourdian G. W., Dean L., Roseman S. The sialic acids. XI. A periodate-resorcinol method for the quantitative estimation of free sialic acids and their glycosides. J Biol Chem. 1971 Jan 25;246(2):430–435. [PubMed] [Google Scholar]
  13. 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]
  14. Langermann S., Palaszynski S. R., Burlein J. E., Koenig S., Hanson M. S., Briles D. E., Stover C. K. Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A. J Exp Med. 1994 Dec 1;180(6):2277–2286. doi: 10.1084/jem.180.6.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Madoff L. C., Hori S., Michel J. L., Baker C. J., Kasper D. L. Phenotypic diversity in the alpha C protein of group B streptococci. Infect Immun. 1991 Aug;59(8):2638–2644. doi: 10.1128/iai.59.8.2638-2644.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Madoff L. C., Michel J. L., Gong E. W., Rodewald A. K., Kasper D. L. Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein. Infect Immun. 1992 Dec;60(12):4989–4994. doi: 10.1128/iai.60.12.4989-4994.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Madoff L. C., Paoletti L. C., Tai J. Y., Kasper D. L. Maternal immunization of mice with group B streptococcal type III polysaccharide-beta C protein conjugate elicits protective antibody to multiple serotypes. J Clin Invest. 1994 Jul;94(1):286–292. doi: 10.1172/JCI117319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marques M. B., Kasper D. L., Shroff A., Michon F., Jennings H. J., Wessels M. R. Functional activity of antibodies to the group B polysaccharide of group B streptococci elicited by a polysaccharide-protein conjugate vaccine. Infect Immun. 1994 May;62(5):1593–1599. doi: 10.1128/iai.62.5.1593-1599.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Michel J. L., Madoff L. C., Kling D. E., Kasper D. L., Ausubel F. M. Cloned alpha and beta C-protein antigens of group B streptococci elicit protective immunity. Infect Immun. 1991 Jun;59(6):2023–2028. doi: 10.1128/iai.59.6.2023-2028.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Michel J. L., Madoff L. C., Olson K., Kling D. E., Kasper D. L., Ausubel F. M. Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10060–10064. doi: 10.1073/pnas.89.21.10060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Michon F., Katzenellenbogen E., Kasper D. L., Jennings H. J. Structure of the complex group-specific polysaccharide of group B Streptococcus. Biochemistry. 1987 Jan 27;26(2):476–486. doi: 10.1021/bi00376a020. [DOI] [PubMed] [Google Scholar]
  22. Musser J. M., Mattingly S. J., Quentin R., Goudeau A., Selander R. K. Identification of a high-virulence clone of type III Streptococcus agalactiae (group B Streptococcus) causing invasive neonatal disease. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4731–4735. doi: 10.1073/pnas.86.12.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Paoletti L. C., Wessels M. R., Rodewald A. K., Shroff A. A., Jennings H. J., Kasper D. L. Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine. Infect Immun. 1994 Aug;62(8):3236–3243. doi: 10.1128/iai.62.8.3236-3243.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pritchard D. G., Gray B. M., Egan M. L. Murine monoclonal antibodies to type Ib polysaccharide of group B streptococci bind to human milk oligosaccharides. Infect Immun. 1992 Apr;60(4):1598–1602. doi: 10.1128/iai.60.4.1598-1602.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stenberg L., O'Toole P., Lindahl G. Many group A streptococcal strains express two different immunoglobulin-binding proteins, encoded by closely linked genes: characterization of the proteins expressed by four strains of different M-type. Mol Microbiol. 1992 May;6(9):1185–1194. doi: 10.1111/j.1365-2958.1992.tb01557.x. [DOI] [PubMed] [Google Scholar]
  26. Stålhammar-Carlemalm M., Stenberg L., Lindahl G. Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections. J Exp Med. 1993 Jun 1;177(6):1593–1603. doi: 10.1084/jem.177.6.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tamura G. S., Kuypers J. M., Smith S., Raff H., Rubens C. E. Adherence of group B streptococci to cultured epithelial cells: roles of environmental factors and bacterial surface components. Infect Immun. 1994 Jun;62(6):2450–2458. doi: 10.1128/iai.62.6.2450-2458.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Wessels M. R., Rubens C. E., Benedí V. J., Kasper D. L. Definition of a bacterial virulence factor: sialylation of the group B streptococcal capsule. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8983–8987. doi: 10.1073/pnas.86.22.8983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zangwill K. M., Schuchat A., Wenger J. D. Group B streptococcal disease in the United States, 1990: report from a multistate active surveillance system. MMWR CDC Surveill Summ. 1992 Nov 20;41(6):25–32. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES