Meningococcal Vaccine Trials

  • Paddy Farrington
  • Elizabeth Miller
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 66)


The evaluation of meningococcal vaccines in humans is a challenging task. Issues of safety, and benefit to the individual patient and to the community may raise difficult ethical problems. The inherent variability of human responses, the rarity of clinical disease, age-dependence in the immune response, and the role of carriers complicates the evaluation process.


Conjugate Vaccine Vaccine Efficacy Protective Efficacy Vaccine Trial Meningococcal Disease 
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  1. 1.
    Farrington, P. and Miller, E. (1996) Clinical Trials, in Methods in Molecular Medicine: Vaccine Protocols (Robinson, A., Farrar, G., and Wiblin, C., eds.), Humana Press, Totowa, NJ, pp. 251–268.CrossRefGoogle Scholar
  2. 2.
    Pocock, S. J. (1983). Clinical Trials: A Practical Approach. Wiley, Chichester, UK.Google Scholar
  3. 3.
    Riedo, F. X., Plikaytis, B. D., and Broome, C. V. (1995) Epidemiology and prevention of meningococcal disease. Pediatr. Infect. Dis. J. 14, 643–657.CrossRefPubMedGoogle Scholar
  4. 4.
    Anon (1997) World Medical Association Declaration of Helsinki. JAMA 277, 925–926.Google Scholar
  5. 5.
    Pocock, S. J. (1993) Statistical and ethical issues in monitoring clinical trials. Stat. Med. 12, 1459–1469.CrossRefPubMedGoogle Scholar
  6. 6.
    Costantino, P., Viti, S., Audino, P., Velmonte, M. A., Nencioni, L., and Rappuoli, R. (1992) Development and phase I clinical testing of a conjugate vaccine against meningococcus A and C. Vaccine 10, 691–698.CrossRefPubMedGoogle Scholar
  7. 7.
    Gold, R., Leplow, M. L., Goldchneider, I., Draper, T. F., and Gotschlich, E. (1979) Kinetics of antibody production to group A and C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children. J. Infect. Dis. 140, 690–697.PubMedGoogle Scholar
  8. 8.
    Richmond, P., Goldblatt, D., Fusco, P. C., et al. (2000) Safety and immunogenicity of a new Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine in healthy adults. Vaccine 18, 641–646.CrossRefGoogle Scholar
  9. 9.
    Miller, E., Richmond, P., Borrow, R., Kaczmarski, E., Cartwright, K., Morris, R., et al. (1998) UK strategy for the introduction of meningococcal C conjugate vaccines. Eleventh International Pathogenic Neisseria Conference, Paris (abstract), p. 57.Google Scholar
  10. 10.
    Goldschneider, I., Gotschlich, E. C., and Artenstein, M. S. (1969) Human immunity to the meningococcus. I. The role of humoral antibodies. J. Exp. Med. 129, 1307–1326.CrossRefPubMedGoogle Scholar
  11. 11.
    Tappero, J. W., Lagos, R., Ballesteros, A. M., et al. (1999) Immunogenicity of 2 serogroup B outer membrane protein meningococcal vaccines. JAMA 281, 1520–1527.CrossRefPubMedGoogle Scholar
  12. 12.
    Lachin, J. M. (1981) Introduction to sample size determination and power analysis for clinical trials. Controlled Clin. Trials 2, 93–113.CrossRefPubMedGoogle Scholar
  13. 13.
    Machin, D. and Campbell, M. J. (1987) Statistical Tables for the Design of Clinical Trials. Blackwell Scientific, Oxford, UK.Google Scholar
  14. 14.
    Bjune, G., Holby, E. A., Gronesby, J. K., et al. (1991) Effect of outer membrane vesicle vaccine against group B meningococcal disease in Norway. Lancet 338, 1093–1096.CrossRefPubMedGoogle Scholar
  15. 15.
    Gotschlich, E. C., Goldschneider, I., and Artenstein, M. S. (1969) Human immunity to the meningococcus V. The effect of immunization with meningococcal group C polysaccharide on the carrier state. J. Exp. Med. 129, 1385–1395.CrossRefPubMedGoogle Scholar
  16. 16.
    Maiden, M. C. J. and Spratt, B. G. (1999) Meningococcal conjugate vaccines: new opportunities and new challenges. Lancet 354, 615–616.CrossRefPubMedGoogle Scholar
  17. 16a.
    Pollard, A. J. and Maiden, M. C. J., eds. Meningococcal Disease (2001) Humana Press, Totowa, NJ, in press.Google Scholar
  18. 17.
    Gustafsson, L., Hallander, H., Olin, P., Reizenstein, E., and Storsaeter, J. (1995) Efficacy trial of acellular pertussis vaccines. Swedish Institute for Infectious Disease Control. Technical report Trial I.Google Scholar
  19. 18.
    Olin, P., Gustafsson Rasmussen, F., Hallander, H., Heijbel, H., and Gottfarb, P. (1997) Efficacy trial of acellular pertussis vaccines. Swedish Institute for Infectious Disease Control. Technical report Trial II.Google Scholar
  20. 19.
    Wahdan, M. H., Rizk, F., El-Akkad, A. M., et al. (1973) A controlled field trial of a serogroup A meningococcal polysaccharide vaccine. WHO Bull. 48, 667–673.Google Scholar
  21. 20.
    Makela, P. H. and Kayhty, H. (1975) Effect of group A meningococcal vaccine in army recruits in Finland. Lancet ii, 883–886.CrossRefGoogle Scholar
  22. 21.
    Devine, L. F., Pierce, W. E., Floyd, T. M., et al. (1970) Evaluation of group C meningococcal polysaccharide vaccine in marine recruits, San Diego, California. Am. J. Epidemiol. 92, 25–32.PubMedGoogle Scholar
  23. 22.
    Halloran, M. E., Haber, M., Longini, I. M., and Struchiner, C. J. (1991) Direct and indirect effects in vaccine efficacy and effectiveness. Am. J. Epidemiol. 133, 323–331.PubMedGoogle Scholar
  24. 23.
    Sierra, G. V. G., Campa, H. C., Varcael, N. M., et al. (1991) Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NIPH Ann. 14, 187–192.Google Scholar
  25. 24.
    Gold, R. and Artenstein, M. S. (1971) Meningococcal Infections 2: Field trial of group C meningococcal polysaccharide vaccine in 1969–70. Bull. WHO 45, 279–282.PubMedGoogle Scholar
  26. 25.
    Artenstein, M. S., Gold, R., Zimmerly, J. G., Wyle, F. A., Schneider, H., and Harkins, C. (1970) Prevention of meningococcal disease by group C polysaccharide vaccine. N. Engl. J. Med. 282, 417–420.CrossRefPubMedGoogle Scholar
  27. 26.
    Peltola, H., Makela, P. H., Kayhty, H., et al. (1977) Clinical efficacy of meningococcus group A capsular polysaccharide vaccine in children three months to five years of age. N. Engl. J. Med. 297, 686–691.CrossRefPubMedGoogle Scholar
  28. 27.
    Fairley, C. K., White, J. M., and Begg, N. T. (1994) Fast-tracking meningococcal vaccination. Lancet 344, 1164–1165.CrossRefPubMedGoogle Scholar
  29. 28.
    Gambian Hepatitis Study Group (1987) The Gambia hepatitis intervention study. Cancer Res. 47, 5782–5787.Google Scholar
  30. 29.
    Hayes, R. J. and Bennett, S. (1999) Simple sample size calculation for cluster-randomized trials. Intl. J. Epidemiol. 28, 319–326.CrossRefGoogle Scholar
  31. 30.
    Taunay, A. E., Feldman, R. A., Bastos, C. O., Galvao, P. A. A., Morais, J. S., and Castro, I. O. (1978) Avaliacao do efeito protetor de vacina polissacaridica antimeningogocica do grupo C, em criancas de 6 a 36 meses. Revista Instit. Adolfo Luz 38, 77–82.Google Scholar
  32. 31.
    Goldschneider, I., Gotschlich, E. C., and Artenstein, M. S. (1969) Human immunity to the meningococcus II. Development of natural immunity. J. Exp. Med. 129, 1327–1348.CrossRefPubMedGoogle Scholar
  33. 32.
    Farrington, C. P. (1992) The measurement and interpretation of age-specific vaccine efficacy. Intl. J. Epidemiol. 21, 1014–1020.CrossRefGoogle Scholar
  34. 33.
    Cornfield, J. (1978) Randomization by group: a formal analysis. Am. J. Epidemiol. 108, 100–102.PubMedGoogle Scholar
  35. 34.
    Bjune, G. (1992) Herd immunity and the meningococcal vaccine trial in Norway. Lancet 340, 315.CrossRefPubMedGoogle Scholar
  36. 35.
    Begg, N. and Miller, E. (1990) Role of epidemiology in vaccine policy. Vaccine 8, 180–189.CrossRefPubMedGoogle Scholar
  37. 36.
    Orenstein, W. A., Bernier, R. H., Dondero, T. J., et al. (1985) Field evaluation of vaccine efficacy. WHO Bull. 63, 1055–1068.Google Scholar
  38. 37.
    Rodrigues, L. C. and Smith, P. G. (1999) Use of the case-control approach in vaccine evaluation: efficacy and adverse effects. Epidemiolog. Rev. 21, 56–72.Google Scholar
  39. 38.
    Farrington, C. P. (1993) Estimation of vaccine effectiveness using the screening method. Intl. J. Epidemiol. 22, 742–746.CrossRefGoogle Scholar
  40. 39.
    Masterton, R. G., Youngs, E. R., Wardle, J. C. R., Croft, K. F., and Jones, D. M. (1988) Control of an outbreak of group C meningococcal meningitis with a polysaccharide vaccine. J. Infect. 17, 177–182.CrossRefPubMedGoogle Scholar
  41. 40.
    Mimouni, D., Gdalevich, M., Mandel, Y., et al. (1998) Meningococcal polysaccharide vaccination of military recruits in Israel: Preliminary assessment of vaccine effect. Scand. J. Infect. Dis. 30, 263–264.CrossRefPubMedGoogle Scholar
  42. 41.
    Kriz, P., Vlckova, J., and Bobak, M. (1995) Targeted vaccination with meningococcal polysaccharide vaccine in one district of the Czech Republic. Epidemiol. Infect. 115, 411–418.Google Scholar
  43. 42.
    De Wals, P., Dionne, M., Douville-Fradet, M., Boulianne, N., Drapeau, J., and De Serres, G. (1996) Impact of a mass immunization campaign against serogroup C meningococcus in the Province of Quebec, Canada. WHO Bull. 74, 407–411.Google Scholar
  44. 43.
    Pintos, A. M. (1998) Evaluacion de la campana de vacunacion de la enfermedad meningococica en Galicia. Metodologia empleada, ventajas e inconvenientes. Estudio de portadores. Rev. Esp. Salud Publica 72, 393–400.Google Scholar
  45. 44.
    Moraes, J. C., Perkins, B. A., Camargo, M. C., et al. (1992) Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet 340, 1074–1078.CrossRefPubMedGoogle Scholar
  46. 45.
    Noronha, C. P., Struchiner, C. J., and Halloran, M. E. (1995) Assessment of the direct effectiveness of BC meningococcal vaccine in Rio de Janeiro, Brazil: a case control study. Intl. J. Epidemiol. 24, 1050–1057.CrossRefGoogle Scholar
  47. 46.
    Fine, P. E. M. and Chen, R. T. (1992) Confounding in studies of adverse reactions to vaccines. Am. J. Epidemiol. 136, 121–135.PubMedGoogle Scholar
  48. 47.
    Farrington, C. P. (1995) Relative incidence estimation from case series for vaccine safety evaluation. Biometrics 51, 228–235.CrossRefPubMedGoogle Scholar
  49. 48.
    Farrington, C. P., Nash, J., and Miller, E. (1996) Case series analysis of adverse reactions to vaccines: a comparative evaluation. Am. J. Epidemiol. 143, 1165–1173.PubMedGoogle Scholar
  50. 49.
    Miller, E., Waight, P., and Farrington, P. (1998) Safety assessment post-licensure. Dev. Biol. Standard. 95, 235–243.Google Scholar
  51. 50.
    Fine, P. E. M. (1993) Herd immunity: History, theory, practice. Epidemiol. Rev. 15, 265–302.PubMedGoogle Scholar
  52. 51.
    Fine, P. E. M. (1991) Meningococcal vaccine trial in Norway. Lancet 338, 1456–1457.CrossRefPubMedGoogle Scholar
  53. 52.
    Sbyrakis, S. and Galanakis, E. (1999) Meningococcal vaccine and herd immunity. Lancet 354, 1733.CrossRefPubMedGoogle Scholar
  54. 53.
    Datta, S., Halloran, M. E., and Longini, I. M. (1999) Efficiency of estimating vaccine efficacy for susceptibility and infectiousness: randomization by individual versus household. Biometrics 55, 792–798.CrossRefPubMedGoogle Scholar
  55. 54.
    Longini, I. R., Sagatelian, K., Rida, W. N., and Halloran, M. E. (1998) Optimal vaccine trial design when estimating vaccine efficacy for susceptibility and infectiousness from multiple populations. Stat. Med. 17, 1121–1136.CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2001

Authors and Affiliations

  • Paddy Farrington
    • 1
  • Elizabeth Miller
    • 2
  1. 1.Department of StatisticsThe Open UniversityMiltonUK
  2. 2.Immunization DivisionPHLS Communicable Disease Surveillance centerLondonUK

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