A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease
J Eskola, H Kayhty, AK Takala, H Peltola, PR Ronnberg, E Kela, E Pekkanen, PH McVerry, and PH Makela
BACKGROUND. Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children. The capsular polysaccharide vaccine does not protect children at greatest risk (those under the age of 18 months), but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group. METHODS. We enrolled 114,000 infants in Finland in an open, prospective, randomized trial of a H. influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]). Children born on odd-numbered days were vaccinated at the ages of 3, 4, 6, and 14 to 18 months; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months. RESULTS. After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination, as compared with 64 cases in the control group, between the ages of approximately 7 and 24 months. The protective efficacy of the vaccine was thus 94 percent (95 percent confidence interval, 83 to 98). No serious adverse effects were reported. The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants. The primary immunization series resulted in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months, and the fourth dose evoked an anamnestic response, with a mean antibody concentration of 45.22 micrograms per milliliter. CONCLUSIONS. A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier (PRP-D), administered to infants beginning at the age of 3 months, is highly effective in protecting young Finnish children (7 to 24 months old) against invasive H. influenzae type b infections.
Source Information
National Public Health Institute, Helsinki, Finland.
This article has been cited by other articles:
Denoel, P. A., Goldblatt, D., de Vleeschauwer, I., Jacquet, J.-M., Pichichero, M. E., Poolman, J. T.
(2007). Quality of the Haemophilus influenzae Type b (Hib) Antibody Response Induced by Diphtheria-Tetanus-Acellular Pertussis/Hib Combination Vaccines. CVI
14: 1362-1369
[Abstract][Full Text]
Torano, G., Toledo, M. E., Baly, A., Fernandez-Santana, V., Rodriguez, F., Alvarez, Y., Serrano, T., Musachio, A., Hernandez, I., Hardy, E., Rodriguez, A., Hernandez, H., Aguilar, A., Sanchez, R., Diaz, M., Muzio, V., Dfana, J., Rodriguez, M. C., Heynngnezz, L., Verez-Bencomo, V.
(2006). Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers.. CVI
13: 1052-1056
[Abstract][Full Text]
Harrison, L. H.
(2006). Prospects for Vaccine Prevention of Meningococcal Infection. Clin. Microbiol. Rev.
19: 142-164
[Abstract][Full Text]
Kelly, D. F., Pollard, A. J., Moxon, E. R.
(2005). Immunological Memory: The Role of B Cells in Long-term Protection Against Invasive Bacterial Pathogens. JAMA
294: 3019-3023
[Abstract][Full Text]
Finn, A, Heath, P
(2005). Conjugate vaccines. Arch. Dis. Child.
90: 667-669
[Full Text]
Segal, S., Pollard, A. J.
(2005). Vaccines against bacterial meningitis. Br Med Bull
72: 65-81
[Abstract][Full Text]
Finn, A.
(2004). Bacterial polysaccharide-protein conjugate vaccines. Br Med Bull
70: 1-14
[Abstract][Full Text]
Artz, A. S., Ershler, W. B., Longo, D. L.
(2003). Pneumococcal Vaccination and Revaccination of Older Adults. Clin. Microbiol. Rev.
16: 308-318
[Abstract][Full Text]
Ragupathi, G., Coltart, D. M., Williams, L. J., Koide, F., Kagan, E., Allen, J., Harris, C., Glunz, P. W., Livingston, P. O., Danishefsky, S. J.
(2002). On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc. Natl. Acad. Sci. USA
99: 13699-13704
[Abstract][Full Text]
Breukels, M. A., Zandvoort, A., van den Dobbelsteen, G. P. J. M., van den Muijsenberg, A., Lodewijk, M. E., Beurret, M., Klok, P. A., Timens, W., Rijkers, G. T.
(2001). Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides. Infect. Immun.
69: 7583-7587
[Abstract][Full Text]
Heath, P. T., Booy, R., Azzopardi, H. J., Slack, M. P. E., Bowen-Morris, J., Griffiths, H., Ramsay, M. E., Deeks, J. J., Moxon, E. R.
(2000). Antibody Concentration and Clinical Protection After Hib Conjugate Vaccination in the United Kingdom. JAMA
284: 2334-2340
[Abstract][Full Text]
Zhang, Q., Choo, S., Everard, J., Jennings, R., Finn, A.
(2000). Mucosal Immune Responses to Meningococcal Group C Conjugate and Group A and C Polysaccharide Vaccines in Adolescents. Infect. Immun.
68: 2692-2697
[Abstract][Full Text]
Peltola, H.
(2000). Worldwide Haemophilus influenzae Type b Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates. Clin. Microbiol. Rev.
13: 302-317
[Abstract][Full Text]
Jefferson, T O, Rabinovich, R., Tuomilehto, J., Bedford, H., Elliman, D., Classen, J. B., Classen, D. C
(1999). Vaccines and their real or perceived adverse effects. BMJ
318: 1487-1487
[Full Text]
Karvonen, M., Cepaitis, Z., Tuomilehto, J.
(1999). Association between type 1 diabetes and Haemophilus influenzae type b vaccination: birth cohort study. BMJ
318: 1169-1172
[Abstract][Full Text]
Breukels, M. A., Rijkers, G. T., Voorhorst-Ogink, M. M., Zegers, B. J. M.
(1999). Regulatory T Cells in the Antibody Response to Haemophilus influenzae Type b Polysaccharide. Infect. Immun.
67: 789-793
[Abstract][Full Text]
Classen, J. B., Classen, D. C
(1999). Public should be told that vaccines may have long term adverse effects. BMJ
318: 193-193
[Full Text]
Jefferson, T.
(1998). Vaccination and its adverse effects: real or perceived. BMJ
317: 159-160
[Full Text]
Vidarsson, G., Sigurdardottir, S. T., Gudnason, T., Kjartansson, S., Kristinsson, K. G., Ingolfsdottir, G., Jonsson, S., Valdimarsson, H., Schiffman, G., Schneerson, R., Jonsdottir, I.
(1998). Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine. Infect. Immun.
66: 2866-2870
[Abstract][Full Text]
Clemens, J., Brenner, R., Rao, M., Tafari, N., Lowe, C.
(1996). Evaluating New Vaccines for Developing Countries: Efficacy or Effectiveness?. JAMA
275: 390-397
[Abstract]
Alho, O.-P., Jokinen, K., Pirila, T., Ilo, A., Oja, H.
(1995). Acute Epiglottitis and Infant Conjugate Haemophilus influenzae Type b Vaccination in Northern Finland. Arch Otolaryngol Head Neck Surg
121: 898-902
[Abstract]
Anderson, E. L., Decker, M. D., Englund, J. A., Edwards, K. M., Anderson, P., Mclnnes, P., Belshe, R. B.
(1995). Interchangeability of Conjugated Haemophilus influenzae Type b Vaccines in Infants. JAMA
273: 849-853
[Abstract]
Fedson, D. S., Shapiro, E. D., LaForce, F. M., Mufson, M. A., Musher, D. M., Spika, J. S., Breiman, R. F., Broome, C. V.
(1994). Pneumococcal Vaccine After 15 Years of Use: Another View. Arch Intern Med
154: 2531-2535
[Abstract]
Peltola, H., Eskola, J., Kayhty, H., Takala, A. K., Makela, P. H.
(1994). Clinical Comparison of the Haemophilus influenzae Type B Polysaccharide-Diphtheria Toxoid and the Oligosaccharide-CRM197 Protein Vaccines in Infancy. Arch Pediatr Adolesc Med
148: 620-625
[Abstract]
Shapiro, E. D.
(1993). Infections Caused by Haemophilus influenzae Type b: The Beginning of the End?. JAMA
269: 264-266
[Abstract]
Eskola, J., Takala, A. K., Kela, E., Pekkanen, E., Kalliokoski, R., Leinonen, M.
(1992). Epidemiology of Invasive Pneumococcal Infections in Children in Finland. JAMA
268: 3323-3327
[Abstract]
Schlesinger, Y., Granoff, D. M., the Vaccine Study Group, , Murphy, T. V., Osterholm, M. T., McHugh, J. E., Anderson, R., Esbenshade, J., Blatter, M., Reisinger, K. S., Keyserling, H., Guito, K., Meschievitz, C. K.
(1992). Avidity and Bactericidal Activity of Antibody Elicited by Different Haemophilus influenzae Type b Conjugate Vaccines. JAMA
267: 1489-1494
[Abstract]
Holmes, S. J., Lucas, A. H., Osterholm, M. T., Froeschle, J. E., Granoff, D. M.
(1991). Immunoglobulin Deficiency and Idiotype Expression in Children Developing Haemophilus influenzae Type b Disease After Vaccination With Conjugate Vaccine. JAMA
266: 1960-1965
[Abstract]
McMillan, J. A., Oski, F. A.
(1991). Pediatrics. JAMA
265: 3156-3158
[Abstract]
Kayhty, H., Eskola, J., Peltola, H., Ronnberg, P-R., Kela, E., Karanko, V., Saarinen, L.
(1991). Antibody Responses to Four Haemophilus influenzae Type b Conjugate Vaccines. Arch Pediatr Adolesc Med
145: 223-227
[Abstract]
(1990). CONJUGATE Hib VACCINE PROTECTS WHITE CHILDREN, BUT NOT ALASKA NATIVES. JWatch General
1990: 6-6
[Full Text]
Ellenberg, S. S., Foulkes, M. A., Midthun, K., Goldenthal, K. L.
(2005). Evaluating the Safety of New Vaccines: Summary of a Workshop. AJPH
95: 800-807
[Abstract][Full Text]