Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1986 Nov;54(2):448–455. doi: 10.1128/iai.54.2.448-455.1986

Rabbit antibodies to the cell wall polysaccharide of Streptococcus pneumoniae fail to protect mice from lethal challenge with encapsulated pneumococci.

S C Szu, R Schneerson, J B Robbins
PMCID: PMC260182  PMID: 3095243

Abstract

A conjugate, composed of the cell wall polysaccharide (C polysaccharide) of Streptococcus pneumoniae and bovine serum albumin (BSA), was prepared with the bifunctional agent N-succinimidyl-3-(2-pyridyldithio)-propionate. Analysis with monoclonal antibodies provided evidence that the phosphocholine (PC) moiety of the C polysaccharide was retained during the conjugation procedure. The C polysaccharide-BSA conjugate elicited antibodies to C polysaccharide in rabbits; no PC-specific antibodies were detected in globulins prepared from these hyperimmune sera obtained early and late after a second immunization. Rabbit hyperimmune sera were taken after multiple intravenous injections of the pneumococcus strain SRC-2, which has a capsulelike structure composed of the C polysaccharide. Globulin prepared from these antisera had both C polysaccharide- and PC-specific antibodies. Antibodies to C polysaccharide elicited by the C polysaccharide-BSA conjugate failed to protect mice against intraperitoneal challenge with a strain of type 3 or type 6A pneumococci. The anti-SRC-2 globulin conferred protection against both of these pneumococcal strains. Absorption of the SRC-2 globulin with C polysaccharide, however, failed to change its protective activity. These data provide evidence that antibodies to the C polysaccharide do not confer immunity against infection of mice with encapsulated pneumococci inoculated by the intraperitoneal route.

Full text

PDF
448

Images in this article

451Image
on p.451
452Image
on p.452
452Image
on p.452

Selected References

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

  1. Au C. C., Einsenstein T. K. Evaluation of the role of the pneumococcal Forssman antigen (F-polysaccharide) in the cross-serotype protection induced by pneumococcal subcellular preparations. Infect Immun. 1981 Jan;31(1):169–173. doi: 10.1128/iai.31.1.169-173.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Au C. C., Eisenstein T. K. Nature of the cross-protective antigen in subcellular vaccines of Streptococcus pneumoniae. Infect Immun. 1981 Jan;31(1):160–168. doi: 10.1128/iai.31.1.160-168.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Austrian R. Some observations on the pneumococcus and on the current status of pneumococcal disease and its prevention. Rev Infect Dis. 1981 Mar-Apr;3 (Suppl):S1–17. doi: 10.1093/clinids/3.supplement_1.s1. [DOI] [PubMed] [Google Scholar]
  4. Bornstein D. L., Schiffman G., Bernheimer H. P., Austrian R. Capsulation of pneumococcus with soluble C-like (Cs) polysaccharide. I. Biological and genetic properties of Cs pneumococcal strains. J Exp Med. 1968 Dec 1;128(6):1385–1400. doi: 10.1084/jem.128.6.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Briles D. E., Claflin J. L., Schroer K., Forman C. Mouse Igg3 antibodies are highly protective against infection with Streptococcus pneumoniae. Nature. 1981 Nov 5;294(5836):88–90. doi: 10.1038/294088a0. [DOI] [PubMed] [Google Scholar]
  6. Briles D. E., Forman C., Hudak S., Claflin J. L. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J Exp Med. 1982 Oct 1;156(4):1177–1185. doi: 10.1084/jem.156.4.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Broome C. V., Facklam R. R., Fraser D. W. Pneumococcal disease after pneumococcal vaccination: an alternative method to estimate the efficacy of pneumococcal vaccine. N Engl J Med. 1980 Sep 4;303(10):549–552. doi: 10.1056/NEJM198009043031003. [DOI] [PubMed] [Google Scholar]
  8. CRESTFIELD A. M., MOORE S., STEIN W. H. The preparation and enzymatic hydrolysis of reduced and S-carboxymethylated proteins. J Biol Chem. 1963 Feb;238:622–627. [PubMed] [Google Scholar]
  9. Carlsson J., Drevin H., Axén R. Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent. Biochem J. 1978 Sep 1;173(3):723–737. doi: 10.1042/bj1730723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chu C., Schneerson R., Robbins J. B., Rastogi S. C. Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates. Infect Immun. 1983 Apr;40(1):245–256. doi: 10.1128/iai.40.1.245-256.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  12. Fong S., Nitecki D. E., Cook R. M., Goodman J. W. Spatial requirements between haptenic and carrier determinants for T-dependent antibody responses. J Exp Med. 1978 Sep 1;148(3):817–822. doi: 10.1084/jem.148.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frasch C. E., Zollinger W. D., Poolman J. T. Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes. Rev Infect Dis. 1985 Jul-Aug;7(4):504–510. doi: 10.1093/clinids/7.4.504. [DOI] [PubMed] [Google Scholar]
  14. Gotschlich E. C., Rey M., Etienne J., Sanborn W. R., Triau R., Cvjetanović B. The immunological responses observed in field studies in Africa with group A meningococcal vaccines. Prog Immunobiol Stand. 1971;5:485–491. [PubMed] [Google Scholar]
  15. Hill W. C., Robbins J. B. Horse anti-pneumococcal immunoglobulins. II. Specific mouse protective activity. Proc Soc Exp Biol Med. 1966 Oct;123(1):105–108. doi: 10.3181/00379727-123-31414. [DOI] [PubMed] [Google Scholar]
  16. Holmberg H., Holme T., Krook A., Olsson T., Sjöberg L., Sjögren A. M. Detection of C polysaccharide in Streptococcus pneumoniae in the sputa of pneumonia patients by an enzyme-linked immunosorbent assay. J Clin Microbiol. 1985 Jul;22(1):111–115. doi: 10.1128/jcm.22.1.111-115.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Holmberg H., Krook A., Sjögren A. M. Determination of antibodies to pneumococcal C polysaccharide in patients with community-acquired pneumonia. J Clin Microbiol. 1985 Nov;22(5):808–814. doi: 10.1128/jcm.22.5.808-814.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jennings H. J., Lugowski C., Young N. M. Structure of the complex polysaccharide C-substance from Streptococcus pneumoniae type 1. Biochemistry. 1980 Sep 30;19(20):4712–4719. doi: 10.1021/bi00561a026. [DOI] [PubMed] [Google Scholar]
  19. Katz M., Papenheimer A. M., Jr Quantitative studies of the specificity of anti-pneumococcal antibodies, types 3 and 8. IV. Binding of labeled hexasaccharides derived from S3 by anti-S3 antibodies and their Fab fragments. J Immunol. 1969 Sep;103(3):491–495. [PubMed] [Google Scholar]
  20. Komatsu T., Lawn C. Y., Amsden A., Leskowitz S. Hapten-specific T cell response to azobenzenearsonate-N-acetyl-L-tyrosine in the Lewis rat. III. Effects of peptide-spacer structure on eliciting ABA-specific helper activity with TNP-haptened ABA-peptide-Ficoll. J Immunol. 1983 Feb;130(2):586–589. [PubMed] [Google Scholar]
  21. Leon M. A., Young N. M. Specificity for phosphorylcholine of six murine myeloma proteins reactive with Pneumococcus C polysaccharide and beta-lipoprotein. Biochemistry. 1971 Apr 13;10(8):1424–1429. doi: 10.1021/bi00784a024. [DOI] [PubMed] [Google Scholar]
  22. McDaniel L. S., Scott G., Kearney J. F., Briles D. E. Monoclonal antibodies against protease-sensitive pneumococcal antigens can protect mice from fatal infection with Streptococcus pneumoniae. J Exp Med. 1984 Aug 1;160(2):386–397. doi: 10.1084/jem.160.2.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mold C., Nakayama S., Holzer T. J., Gewurz H., Du Clos T. W. C-reactive protein is protective against Streptococcus pneumoniae infection in mice. J Exp Med. 1981 Nov 1;154(5):1703–1708. doi: 10.1084/jem.154.5.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mufson M. A., Oley G., Hughey D. Pneumococcal disease in a medium-sized community in the United States. JAMA. 1982 Sep 24;248(12):1486–1489. [PubMed] [Google Scholar]
  25. Mäkelä P. H., Leinonen M., Pukander J., Karma P. A study of the pneumococcal vaccine in prevention of clinically acute atttacks of recurrent otitis media. Rev Infect Dis. 1981 Mar-Apr;3 (Suppl):S124–S132. doi: 10.1093/clinids/3.supplement_1.s124. [DOI] [PubMed] [Google Scholar]
  26. Oliveira E. B., Gotschlich E. C., Liu T. Y. Comparative studies on the binding properties of human and rabbit C-reactive proteins. J Immunol. 1980 Mar;124(3):1396–1402. [PubMed] [Google Scholar]
  27. Paton J. C., Lock R. A., Hansman D. J. Effect of immunization with pneumolysin on survival time of mice challenged with Streptococcus pneumoniae. Infect Immun. 1983 May;40(2):548–552. doi: 10.1128/iai.40.2.548-552.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pedersen F. K., Henrichsen J., Sørensen U. S., Nielsen J. L. Anti-C-carbohydrate antibodies after pneumococcal vaccination. Acta Pathol Microbiol Immunol Scand C. 1982 Dec;90(6):353–355. doi: 10.1111/j.1699-0463.1982.tb01462.x. [DOI] [PubMed] [Google Scholar]
  29. Robbins J. B., Austrian R., Lee C. J., Rastogi S. C., Schiffman G., Henrichsen J., Mäkelä P. H., Broome C. V., Facklam R. R., Tiesjema R. H. Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis. 1983 Dec;148(6):1136–1159. doi: 10.1093/infdis/148.6.1136. [DOI] [PubMed] [Google Scholar]
  30. Siber G. R., Weitzman S. A., Aisenberg A. C., Weinstein H. J., Schiffman G. Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease. N Engl J Med. 1978 Aug 31;299(9):442–448. doi: 10.1056/NEJM197808312990903. [DOI] [PubMed] [Google Scholar]
  31. Szu S. C., Clarke S., Robbins J. B. Protection against pneumococcal infection in mice conferred by phosphocholine-binding antibodies: specificity of the phosphocholine binding and relation to several types. Infect Immun. 1983 Feb;39(2):993–999. doi: 10.1128/iai.39.2.993-999.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sørensen U. B., Agger R., Bennedsen J., Henrichsen J. Phosphorylcholine determinants in six pneumococcal capsular polysaccharides detected by monoclonal antibody. Infect Immun. 1984 Mar;43(3):876–878. doi: 10.1128/iai.43.3.876-878.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sørensen U. B., Henrichsen J. C-polysaccharide in a pneumococcal vaccine. Acta Pathol Microbiol Immunol Scand C. 1984 Dec;92(6):351–356. doi: 10.1111/j.1699-0463.1984.tb00099.x. [DOI] [PubMed] [Google Scholar]
  34. Vaitukaitis J., Robbins J. B., Nieschlag E., Ross G. T. A method for producing specific antisera with small doses of immunogen. J Clin Endocrinol Metab. 1971 Dec;33(6):988–991. doi: 10.1210/jcem-33-6-988. [DOI] [PubMed] [Google Scholar]
  35. Wallick S., Claflin J. L., Briles D. E. Resistance to Streptococcus pneumoniae is induced by a phosphocholine-protein conjugate. J Immunol. 1983 Jun;130(6):2871–2875. [PubMed] [Google Scholar]
  36. Wang L. Y., Frasch C. E. Development of a Neisseria meningitidis group B serotype 2b protein vaccine and evaluation in a mouse model. Infect Immun. 1984 Nov;46(2):408–414. doi: 10.1128/iai.46.2.408-414.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yother J., Forman C., Gray B. M., Briles D. E. Protection of mice from infection with Streptococcus pneumoniae by anti-phosphocholine antibody. Infect Immun. 1982 Apr;36(1):184–188. doi: 10.1128/iai.36.1.184-188.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yurchak A. M., Austrian R. Serologic and genetic relationships between pneumococci and other respiratory streptococci. Trans Assoc Am Physicians. 1966;79:368–375. [PubMed] [Google Scholar]

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

RESOURCES