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Volume 47, Issue 7

Recent developments in bacterial conjugate vaccines Free

Abstract

Study of the epidemiology of childhood infection reveals that the brunt of disease for a number of invasive bacterial infections is borne by children under the age of 4 years. type b (Hib), and , the three most important causes of childhood meningitis, illustrate this phenomenon, which is caused by the inability of infants and young children to mount antibodies to the carbohydrates that form a capsule surrounding these organisms. Carbohydrates are traditionally viewed as T-independent antigens with a number of unique and important immunological properties that are not encountered when inducing an immune response to proteins. These properties include no overt requirement for the presence of T cells to induce an immune response, dominance of IgM, failure to induce memory following immunisation, an absence of affinity maturation following immunisation, and poor immunogenicity in infants, the elderly and the immunocompromised. These properties of carbohydrates have precluded the use of pure carbohydrate vaccines in those patients most at risk. Conjugate vaccine technology, where a carbohydrate antigen is coupled chemically to a protein carrier, has overcome the limitations of carbohydrates as vaccine antigens by rendering the carbohydrate moiety of such vaccines immunogenic, even in the very young. The dramatic success of the Hib conjugate vaccines, the first conjugates licensed clinically for human use, in reducing the incidence of invasive Hib disease has demonstrated the potential value of such conjugate vaccines. Similar technology is, therefore, being applied to a number of other vaccines in development, including (groups A and C) and vaccines. The large number of pneumococcal carbohydrate serotypes that require inclusion in a vaccine makes this conjugate formulation far more complicated than that for Hib, and it is likely that the dramatic success of the Hib conjugate vaccines will be more difficult to repeat for the pneumococcus.

  • Received:
  • Accepted:
  • Published Online:
© 1998 The Pathological Society of Great Britain and Ireland
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1998-07-01
2024-04-26
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References

  1. 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; 50:533–550
     [Google Scholar]
  2. Baker P. J. T. cell regulation of the antibody response to bacterial polysaccharide antigens: an examination of some general characteristics and their implications. J Infect Dis 1992; 165: Suppl 1S44–48
     [Google Scholar]
  3. Peltola H., Käyhty H., Sivonen A., Mäkelä H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977; 60:730–737
     [Google Scholar]
  4. Käyhty H., Karanko V., Peltola H., Mäkelä P. H. Serum antibodies after vaccination with Haemophilus influenzae type b capsular polysaccharide and responses to reimmunization: no evidence of immunologic tolerance or memory. Pediatrics 1984; 74:857–865
     [Google Scholar]
  5. Zahradnik J. M., Gordon L. K. Augmented antibody [Ab] responses in infants administered a new Haemophilus influenzae type b capsular polysaccharide [PRP] diphtheria toxoid conjugate vaccine [PRP-D]. Pediatr Res 1984; 18:289A
     [Google Scholar]
  6. Ward J., Berkowitz C., Pescetti J., Burkart K., Samuelson J., Gordon L. Enhanced immunogenicity in young infants of a new Haemophilus influenzae type b (HIB) capsular polysaccharide (PRP)-diphtheria toxoid (D) conjugate vaccine. Pediatr Res 1984; 18:287A
     [Google Scholar]
  7. Granoff D. M., Anderson E. L., Osterholm M. T. Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants. J Pediatr 1992; 121:187–194
     [Google Scholar]
  8. Käyhty H., Eskola J., Peltola H., Saarinen L., Mäkelä P. H. High antibody responses to booster doses of either Haemophilus influenzae capsular polysaccharides or conjugate vaccine after primary immunization with conjugate vaccines. J Infect Dis 1992; 165: Suppl 1S165–166
     [Google Scholar]
  9. Zepp F., Schmitt H. J., Kaufhold A. Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine. Eur J Pediatr 1997; 156:18–24
     [Google Scholar]
  10. Goldblatt D., Pinto Vas R., Miller E. Antibody avidity as a surrogate marker of successful priming following Haemophilus influenzae type b conjugate vaccine. J Infect Dis 1997 (in press)
    [Google Scholar]
  11. Peltola H., Kilpi T., Anttila M. Rapid disappearance of Haemophilus influenzae type b meningitis after routine childhood immunisation with conjugate vaccines. Lancet 1992; 340:592–594
     [Google Scholar]
  12. Ambrosino D. M., Sood S., Lee M. C. IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in infants. Pediatr Infect Dis J 1992; 11:855–859
     [Google Scholar]
  13. Goldblatt D., Fairley C. K., Cartwright K., Miller E. Interchangeability of conjugated Haemophilus influenzae type b vaccines during the primary immunisation of infants. BMJ 1996; 312:817–818
     [Google Scholar]
  14. Lieberman J. M., Greenberg D. P., Wong V. K. Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines. J Pediatr 1995; 126:198–205
     [Google Scholar]
  15. Barington T., Gyhrs A., Kristensen K., Heilmann C. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine. Infect Immun 1994; 62:9–14
     [Google Scholar]
  16. Santosham M., Wolff M., Reid R. The efficacy in Navajo infants of conjugate vaccine consisting of Haemophilus influenza type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. N Engl J Med 1991; 324:1767–1772
     [Google Scholar]
  17. Booy R., Heath P. T., Slack M. P. E., Begg N., Moxon E. R. Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster. Lancet 1997; 349:1197–1202
     [Google Scholar]
  18. Mulholland K., Hilton S., Adegbola R. Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants. Lancet 1997; 349:1191–1197
     [Google Scholar]
  19. Eskola J., Olander R., Hovi T., Litmanen L., Peltola S., Käyhty H. Randomised trial of the effect of co-administration with acellular pertussis DTP vaccine on immunogenicity of Haemophilus influenzae type b conjugate vaccine. Lancet 1996; 348:1688–1692
     [Google Scholar]
  20. Mills E. L., Russell M., Cunning L. A fully liquid acellular pertussis vaccine combined with IPV and Hib vaccines (DTaP-IPV-PRP-T) is safe and immunogenic without significant interaction. ICAAC 1997 G-95 [Abstract]
    [Google Scholar]
  21. Twumasi P. A., Kumah S., Leach A. A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants. J Infect Dis 1995; 171:632–638
     [Google Scholar]
  22. Fairley C. K., Begg N., Borrow R., Fox A. J., Jones D. M., Cartwright K. Conjugate meningococcal serogroup A and C vaccine: reactogenicity and immunogenicity in United Kingdom infants. J Infect Dis 1996; 174:1360–1363
     [Google Scholar]
  23. Fusco P. C., Michon F., Tai J. Y., Blake M. S. Preclinical evaluation of a novel group B meningococcal conjugate vaccine that elicits bactericidal activity in both mice and nonhuman primates. J Infect Dis 1997; 175:364–372
     [Google Scholar]
  24. George R. C., Ball L. C., Cooper P. G. Antibiotic-resistant pneumococci in the United Kingdom. Commun Dis Rep CDR Rev 1992; 2:R37–43
     [Google Scholar]
  25. Simberkoff M. S. Drug-resistant pneumococcal infections in the United States. A problem for clinicians, laboratories, and public health. JAMA 1994; 271:1875–1876
     [Google Scholar]
  26. Privitera G. Penicillin resistance among Streptococcus pneumoniae in Europe. Diagn Microbiol Infect Dis 1994; 19:157–161
     [Google Scholar]
  27. Simberkoff M. S., Cross A. P., Al-Ibrahim M. Efficacy of pneumococcal vaccine in high-risk patients: results of a Veterans Administration cooperative study. N Engl J Med 1986; 315:1318–1327
     [Google Scholar]
  28. Shapiro E. D., Berg A. T., Austrian R. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991; 325:1453–1460
     [Google Scholar]
  29. Scott J. A. G., Hall A. J., Dagan R. Serogroup-specific epidemiology of Streptococcus pneumoniae-, associations with age, sex, and geography in 7,000 episodes of invasive disease. Clin Infect Dis 1996; 22:973–981
     [Google Scholar]
  30. Sniadack D. H., Schwartz B., Lipman H. Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children - implications for vaccine strategies. Pediatr Infect Dis J 1995; 14:503–510
     [Google Scholar]
  31. Greenwood B. M., Hassan-King M., Macfarlane J. T. Pneumococcal serotypes in West Africa. Lancet 1980; 1:360
     [Google Scholar]
  32. Mastro T. D., Ghafoor A., Nomani N. K. Antimicrobial resistance of pneumococci in children with acute lower respiratory tract infection in Pakistan. Lancet 1991; 337:156–159
     [Google Scholar]
  33. Leach A., Ceesay S. J., Banya W. A. S., Greenwood B. M. Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate vaccine in Gambian infants. Pediatr Infect Dis J 1996; 15:333–339
     [Google Scholar]
  34. Åhman H., Käyhty H., Tamminen P., Vuorela A., Malinoski F., Eskola J. Pentavalent pneumococcal oligosaccharide conjugate vaccine PncCRM is well tolerated and able to induce an antibody response in infants. Pediatr Infect Dis J 1996; 15:134–139
     [Google Scholar]
  35. Pichichero M. E., Shelly M. A., Treanor J. J. Evaluation of a pentavalent conjugated pneumococcal vaccine in toddlers. Pediatr Infect Dis J 1997; 16:72–74
     [Google Scholar]
  36. Anderson E. L., Kennedy D. J., Geldmacher K. M., Donnelly J., Mendelman P. M. Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants. J Pediatr 1996; 128:649–653
     [Google Scholar]
  37. O’Brien K. L., Steinhoff M. C., Edwards K., Keyserling H., Thoms M. L., Madore D. Immunologic priming of young children by pneumococcal glycoprotein conjugate, but not polysaccharide, vaccines. Pediatr Infect Dis J 1996; 15:425–430
     [Google Scholar]
  38. King J. C., Vink P. E., Farley J. J. Comparison of the safety and immunogenicity of a pneumococcal conjugate with a licensed polysaccharide vaccine in human immunodeficiency virus and non-human immunodeficiency virus-infected children. Pediatr Infect Dis J 1996; 15:192–196
     [Google Scholar]
  39. Dagan R., Melamed R., Muallem M. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J Infect Dis 1996; 174:1271–1278
     [Google Scholar]
  40. Obaro S. K., Adegbola R. A., Banya W. A. S., Greenwood B. M. Carriage of pneumococci after pneumococcal vaccination. Lancet 1996; 348:271–272
     [Google Scholar]
  41. Mbelle N., Wasas A., Huebner R., Kimura A., Chang I., Klugman K. Immunogenicity and impact on carriage of 9-valent pneumococcal conjugate vaccine given to infants in Soweto, South Africa. ICAAC 1997 LB21 [Abstract]
    [Google Scholar]
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