Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1992 May;60(5):1826–1833. doi: 10.1128/iai.60.5.1826-1833.1992

Synthetic trimer and tetramer of 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate conjugated to protein induce antibody responses to Haemophilus influenzae type b capsular polysaccharide in mice and monkeys.

C C Peeters 1, D Evenberg 1, P Hoogerhout 1, H Käyhty 1, L Saarinen 1, C A van Boeckel 1, G A van der Marel 1, J H van Boom 1, J T Poolman 1
PMCID: PMC257080  PMID: 1563770

Abstract

Synthetic oligosaccharides derived from the capsular polysaccharide (PRP) of Haemophilus influenzae type b were conjugated to carrier proteins via a thioether linkage. Conjugates were made of trimeric and tetrameric ribose-ribitol-phosphate and tetanus toxoid or diphtheria toxin. All conjugates elicited anti-PRP antibody responses with an increasing immunoglobulin G/immunoglobulin M ratio in adult mice and monkeys. Trimer conjugates elicited lower anti-PRP antibody responses compared with tetramer conjugates. Adult monkeys responded equally well to the tetrameric oligosaccharide-tetanus toxoid conjugate as to the oligosaccharide-CRM197 conjugate (HbOC), which elicits protective levels of serum antibodies in human infants after two or three injections.

Full text

PDF
1826

Selected References

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

  1. Anderson P. W., Pichichero M. E., Insel R. A., Betts R., Eby R., Smith D. H. Vaccines consisting of periodate-cleaved oligosaccharides from the capsule of Haemophilus influenzae type b coupled to a protein carrier: structural and temporal requirements for priming in the human infant. J Immunol. 1986 Aug 15;137(4):1181–1186. [PubMed] [Google Scholar]
  2. Anderson P. W., Pichichero M. E., Stein E. C., Porcelli S., Betts R. F., Connuck D. M., Korones D., Insel R. A., Zahradnik J. M., Eby R. Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197. J Immunol. 1989 Apr 1;142(7):2464–2468. [PubMed] [Google Scholar]
  3. Anderson P., Pichichero M., Edwards K., Porch C. R., Insel R. Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine. J Pediatr. 1987 Nov;111(5):644–650. doi: 10.1016/s0022-3476(87)80237-8. [DOI] [PubMed] [Google Scholar]
  4. Avery O. T., Goebel W. F. CHEMO-IMMUNOLOGICAL STUDIES ON CONJUGATED CARBOHYDRATE-PROTEINS : II. IMMUNOLOGICAL SPECIFICITY OF SYNTHETIC SUGAR-PROTEIN ANTIGENS. J Exp Med. 1929 Sep 30;50(4):533–550. doi: 10.1084/jem.50.4.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beuvery E. C., van Rossum F., Nagel J. Comparison of the induction of immunoglobulin M and G antibodies in mice with purified pneumococcal type 3 and meningococcal group C polysaccharides and their protein conjugates. Infect Immun. 1982 Jul;37(1):15–22. doi: 10.1128/iai.37.1.15-22.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claesson B. A., Schneerson R., Robbins J. B., Johansson J., Lagergard T., Taranger J., Bryla D., Levi L., Cramton T., Trollfors B. Protective levels of serum antibodies stimulated in infants by two injections of Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate. J Pediatr. 1989 Jan;114(1):97–100. doi: 10.1016/s0022-3476(89)80611-0. [DOI] [PubMed] [Google Scholar]
  7. Crisel R. M., Baker R. S., Dorman D. E. Capsular polymer of Haemophilus influenzae, type b. I. Structural characterization of the capsular polymer of strain Eagan. J Biol Chem. 1975 Jul 10;250(13):4926–4930. [PubMed] [Google Scholar]
  8. Eskola J., Peltola H., Takala A. K., Käyhty H., Hakulinen M., Karanko V., Kela E., Rekola P., Rönnberg P. R., Samuelson J. S. Efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy. N Engl J Med. 1987 Sep 17;317(12):717–722. doi: 10.1056/NEJM198709173171201. [DOI] [PubMed] [Google Scholar]
  9. Granoff D. M., Boies E. G., Munson R. S., Jr Immunogenicity of Haemophilus influenzae type b polysaccharide--diphtheria toxoid conjugate vaccine in adults. J Pediatr. 1984 Jul;105(1):22–27. doi: 10.1016/s0022-3476(84)80350-9. [DOI] [PubMed] [Google Scholar]
  10. Halsey N. A., Johansen T. L., Bowman L. C., Glode M. P. Evaluation of the protective efficacy of Haemophilus influenzae type b vaccines in an animal model. Infect Immun. 1983 Mar;39(3):1196–1200. doi: 10.1128/iai.39.3.1196-1200.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hetherington S. V. The intrinsic affinity constant (K) of anticapsular antibody to oligosaccharides of Haemophilus influenzae type b. J Immunol. 1988 Jun 1;140(11):3966–3970. [PubMed] [Google Scholar]
  12. Käyhty H., Eskola J., Peltola H., Stout M. G., Samuelson J. S., Gordon L. K. Immunogenicity in infants of a vaccine composed of Haemophilus influenzae type b capsular polysaccharide mixed with DPT or conjugated to diphtheria toxoid. J Infect Dis. 1987 Jan;155(1):100–106. doi: 10.1093/infdis/155.1.100. [DOI] [PubMed] [Google Scholar]
  13. Lenoir A. A., Granoff P. D., Granoff D. M. Immunogenicity of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in 2- to 6-month-old infants. Pediatrics. 1987 Aug;80(2):283–287. [PubMed] [Google Scholar]
  14. Lepow M. L., Samuelson J. S., Gordon L. K. Safety and immunogenicity of Haemophilus influenzae type B polysaccharide-diphtheria toxoid conjugate vaccine in adults. J Infect Dis. 1984 Sep;150(3):402–406. doi: 10.1093/infdis/150.3.402. [DOI] [PubMed] [Google Scholar]
  15. Meuwissen J. H., Tauber I., Leeuwenberg A. D., Beckers P. J., Sieben M. Parasitologic and serologic observations of infection with Pneumocystis in humans. J Infect Dis. 1977 Jul;136(1):43–49. doi: 10.1093/infdis/136.1.43. [DOI] [PubMed] [Google Scholar]
  16. Munson R. S., Jr, Kabeer M. H., Lenoir A. A., Granoff D. M. Epidemiology and prospects for prevention of disease due to Haemophilus influenzae in developing countries. Rev Infect Dis. 1989 May-Jun;11 (Suppl 3):S588–S597. doi: 10.1093/clinids/11.supplement_3.s588. [DOI] [PubMed] [Google Scholar]
  17. Peltola H., Käyhty H., Virtanen M., Mäkelä P. H. Prevention of Hemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med. 1984 Jun 14;310(24):1561–1566. doi: 10.1056/NEJM198406143102404. [DOI] [PubMed] [Google Scholar]
  18. Robbins J. B., Parke J. C., Jr, Schneerson R., Whisnant J. K. Quantitative measurement of "natural" and immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies. Pediatr Res. 1973 Mar;7(3):103–110. doi: 10.1203/00006450-197303000-00001. [DOI] [PubMed] [Google Scholar]
  19. Schneerson R., Barrera O., Sutton A., Robbins J. B. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J Exp Med. 1980 Aug 1;152(2):361–376. doi: 10.1084/jem.152.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schneerson R., Robbins J. B., Chu C., Sutton A., Vann W., Vickers J. C., London W. T., Curfman B., Hardegree M. C., Shiloach J. Serum antibody responses of juvenile and infant rhesus monkeys injected with Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-protein conjugates. Infect Immun. 1984 Sep;45(3):582–591. doi: 10.1128/iai.45.3.582-591.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schreiber J. R., Barrus V., Cates K. L., Siber G. R. Functional characterization of human IgG, IgM, and IgA antibody directed to the capsule of Haemophilus influenzae type b. J Infect Dis. 1986 Jan;153(1):8–16. doi: 10.1093/infdis/153.1.8. [DOI] [PubMed] [Google Scholar]
  22. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  23. Vella P. P., Ellis R. W. Immunogenicity of Haemophilus influenzae type b conjugate vaccines in infant rhesus monkeys. Pediatr Res. 1991 Jan;29(1):10–13. doi: 10.1203/00006450-199101000-00003. [DOI] [PubMed] [Google Scholar]

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

RESOURCES