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. 1992 Dec;60(12):4977–4983. doi: 10.1128/iai.60.12.4977-4983.1992

Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.

P P Vella 1, S Marburg 1, J M Staub 1, P J Kniskern 1, W Miller 1, A Hagopian 1, C Ip 1, R L Tolman 1, C M Rusk 1, L S Chupak 1, et al.
PMCID: PMC258265  PMID: 1452327

Abstract

In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants.

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Selected References

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  1. Ahonkhai V. I., Lukacs L. J., Jonas L. C., Matthews H., Vella P. P., Ellis R. W., Staub J. M., Dolan K. T., Rusk C. M., Calandra G. B. Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation. Pediatrics. 1990 Apr;85(4 Pt 2):676–681. [PubMed] [Google Scholar]
  2. Anderson P. Antibody responses to Haemophilus influenzae type b and diphtheria toxin induced by conjugates of oligosaccharides of the type b capsule with the nontoxic protein CRM197. Infect Immun. 1983 Jan;39(1):233–238. doi: 10.1128/iai.39.1.233-238.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Austrian R., Howie V. M., Ploussard J. H. The bacteriology of pneumococcal otitis media. Johns Hopkins Med J. 1977 Sep;141(3):104–111. [PubMed] [Google Scholar]
  4. Black S. B., Shinefield H. R., Fireman B., Hiatt R., Polen M., Vittinghoff E. Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61,080 children. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group. Pediatr Infect Dis J. 1991 Feb;10(2):97–104. doi: 10.1097/00006454-199102000-00004. [DOI] [PubMed] [Google Scholar]
  5. Bolan G., Broome C. V., Facklam R. R., Plikaytis B. D., Fraser D. W., Schlech W. F., 3rd Pneumococcal vaccine efficacy in selected populations in the United States. Ann Intern Med. 1986 Jan;104(1):1–6. doi: 10.7326/0003-4819-104-1-1. [DOI] [PubMed] [Google Scholar]
  6. Borgoño J. M., McLean A. A., Vella P. P., Woodhour A. F., Canepa I., Davidson W. L., Hilleman M. R. Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants. Proc Soc Exp Biol Med. 1978 Jan;157(1):148–154. doi: 10.3181/00379727-157-40010. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Douglas R. M., Paton J. C., Duncan S. J., Hansman D. J. Antibody response to pneumococcal vaccination in children younger than five years of age. J Infect Dis. 1983 Jul;148(1):131–137. doi: 10.1093/infdis/148.1.131. [DOI] [PubMed] [Google Scholar]
  9. Fattom A., Vann W. F., Szu S. C., Sutton A., Li X., Bryla D., Schiffman G., Robbins J. B., Schneerson R. Synthesis and physicochemical and immunological characterization of pneumococcus type 12F polysaccharide-diphtheria toxoid conjugates. Infect Immun. 1988 Sep;56(9):2292–2298. doi: 10.1128/iai.56.9.2292-2298.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Giebink G. S., Foker J. E., Kim Y., Schiffman G. Serum antibody and opsonic responses to vaccination with pneumococcal capsular polysaccharide in normal and splenectomized children. J Infect Dis. 1980 Mar;141(3):404–412. doi: 10.1093/infdis/141.3.404. [DOI] [PubMed] [Google Scholar]
  11. Giebink G. S., Ripley-Petzoldt M. L., Juhn S. K., Aeppli D., Tomasz A., Tuomanen E. Contribution of pneumococcal cell wall to experimental otitis media pathogenesis. Ann Otol Rhinol Laryngol Suppl. 1988 May-Jun;132:28–30. doi: 10.1177/00034894880970s308. [DOI] [PubMed] [Google Scholar]
  12. Giebink G. S., Schiffman G., Petty K., Quie P. G. Modification of otitis media following vaccination with the capsular polysaccharide of Streptococcus pneumoniae in chinchillas. J Infect Dis. 1978 Oct;138(4):480–487. doi: 10.1093/infdis/138.4.480. [DOI] [PubMed] [Google Scholar]
  13. Giebink G. S., Verhoef J., Peterson P. K., Quie P. G. Opsonic requirements for phagocytosis of Streptococcus pneumoniae types VI, XVIII, XXIII, and XXV. Infect Immun. 1977 Nov;18(2):291–297. doi: 10.1128/iai.18.2.291-297.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gray B. M., Converse G. M., 3rd, Dillon H. C., Jr Serotypes of Streptococcus pneumoniae causing disease. J Infect Dis. 1979 Dec;140(6):979–983. doi: 10.1093/infdis/140.6.979. [DOI] [PubMed] [Google Scholar]
  15. Gray B. M., Dillon H. C., Jr Clinical and epidemiologic studies of pneumococcal infection in children. Pediatr Infect Dis. 1986 Mar-Apr;5(2):201–207. doi: 10.1097/00006454-198603000-00009. [DOI] [PubMed] [Google Scholar]
  16. Gray B. M. Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate). Pediatrics. 1990 Apr;85(4 Pt 2):694–697. [PubMed] [Google Scholar]
  17. Helting T. B., Guthöhrlein G., Blackkolb F., Ronneberger H. Serotype determinant protein of Neisseria Meningitidis. Large scale preparation by direct detergent treatment of the bacterial cells. Acta Pathol Microbiol Scand C. 1981 Apr;89(2):69–78. [PubMed] [Google Scholar]
  18. Hilleman M. R., McLean A. A., Vella P. P., Weibel R. E., Woodhour A. F. Polyvalent pneumococcal polysaccharide vaccines. Bull World Health Organ. 1978;56(3):371–375. [PMC free article] [PubMed] [Google Scholar]
  19. Howie V. M. Natural history of otitis media. Ann Otol Rhinol Laryngol. 1975 Mar-Apr;84(2 PT2):67–72. doi: 10.1177/00034894750840S215. [DOI] [PubMed] [Google Scholar]
  20. Jennings H. J., Lugowski C., Ashton F. E. Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis. Infect Immun. 1984 Jan;43(1):407–412. doi: 10.1128/iai.43.1.407-412.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Klein J. O. The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis. 1981 Mar-Apr;3(2):246–253. doi: 10.1093/clinids/3.2.246. [DOI] [PubMed] [Google Scholar]
  22. Koskela M. Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination. Pediatr Infect Dis J. 1987 Jun;6(6):519–526. doi: 10.1097/00006454-198706000-00006. [DOI] [PubMed] [Google Scholar]
  23. Leinonen M., Säkkinen A., Kalliokoski R., Luotonen J., Timonen M., Mäkelä P. H. Antibody response to 14-valent pneumococcal capsular polysaccharide vaccine in pre-school age children. Pediatr Infect Dis. 1986 Jan-Feb;5(1):39–44. doi: 10.1097/00006454-198601000-00008. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Paton J. C., Lock R. A., Lee C. J., Li J. P., Berry A. M., Mitchell T. J., Andrew P. W., Hansman D., Boulnois G. J. Purification and immunogenicity of genetically obtained pneumolysin toxoids and their conjugation to Streptococcus pneumoniae type 19F polysaccharide. Infect Immun. 1991 Jul;59(7):2297–2304. doi: 10.1128/iai.59.7.2297-2304.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Paton J. C., Toogood I. R., Cockington R. A., Hansman D. Antibody response to pneumococcal vaccine in children aged 5 to 15 years. Am J Dis Child. 1986 Feb;140(2):135–138. doi: 10.1001/archpedi.1986.02140160053031. [DOI] [PubMed] [Google Scholar]
  27. Salerno R. A., Odell C., McCauley J., Mancinelli R., Morges W., Gray A. Quantitative analysis of 23-valent 'Pneumovax' by automated rate nephelometry. J Biol Stand. 1984 Oct;12(4):447–450. doi: 10.1016/s0092-1157(84)80069-4. [DOI] [PubMed] [Google Scholar]
  28. Santosham M., Wolff M., Reid R., Hohenboken M., Bateman M., Goepp J., Cortese M., Sack D., Hill J., Newcomer W. The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. N Engl J Med. 1991 Jun 20;324(25):1767–1772. doi: 10.1056/NEJM199106203242503. [DOI] [PubMed] [Google Scholar]
  29. Schiffman G., Douglas R. M., Bonner M. J., Robbins M., Austrian R. A radioimmunoassay for immunologic phenomena in pneumococcal disease and for the antibody response to pneumococcal vaccines. I. Method for the radioimmunoassay of anticapsular antibodies and comparison with other techniques. J Immunol Methods. 1980;33(2):133–144. doi: 10.1016/s0022-1759(80)80004-4. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Smit P., Oberholzer D., Hayden-Smith S., Koornhof H. J., Hilleman M. R. Protective efficacy of pneumococcal polysaccharide vaccines. JAMA. 1977 Dec 12;238(24):2613–2616. [PubMed] [Google Scholar]
  32. Tai J. Y., Vella P. P., McLean A. A., Woodhour A. F., McAleer W. J., Sha A., Dennis-Sykes C., Hilleman M. R. Haemophilus influenzae type b polysaccharide-protein conjugate vaccine. Proc Soc Exp Biol Med. 1987 Feb;184(2):154–161. doi: 10.3181/00379727-184-42460. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Vella P. P., McLean A. A., Woodhour A. F., Weibel R. E., Hilleman M. R. Persistence of Pneumococcal antibodies in human subjects following vaccination. Proc Soc Exp Biol Med. 1980 Sep;164(4):435–438. doi: 10.3181/00379727-164-40891. [DOI] [PubMed] [Google Scholar]
  35. Vella P. P., Staub J. M., Armstrong J., Dolan K. T., Rusk C. M., Szymanski S., Greer W. E., Marburg S., Kniskern P. J., Schofield T. L. Immunogenicity of a new Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB). Pediatrics. 1990 Apr;85(4 Pt 2):668–675. [PubMed] [Google Scholar]

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