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Capsular polysaccharide–carrier protein conjugated vaccines against Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae
Mark A. Fletcher, M.D.
Wyeth Vaccines, Paris, France

   Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae cause the serious bacterial infections of childhood: meningitis, bacteremia / sepsis, pneumonia, and otitis media / sinusitis. The capsular polysaccharide–carrier protein conjugated vaccines are highly effective against these pathogens, protecting children with a clinical efficacy of at least 90% against meningitis and bacteremia/sepsis. By chemically linking the capsular polysaccharide of the vaccine target to a carrier protein like CRM197 (a genetically-modified, and non-toxic, form of the diphtheria toxin), this class of vaccine induces strong antibody responses in infants, providing high-avidity antibodies that are bactericidal. Furthermore, and in contrast to the plain polysaccharide vaccines, the capsular polysaccharide–carrier protein conjugated vaccines provide an immunized child with a persistent state of immunologic memory, giving long-term protection against infection and disease. The public health impact of capsular polysaccharide–carrier protein conjugated vaccines have been remarkable.

   For instance, the number of invasive Hib disease cases in the USA plunged from about 20,000 cases before introduction of the Haemophilus influenzae type b (Hib) vaccines to 54 cases reported in 1998 (i.e., 100 per 100,000 to < 0.3 per 100,000).

   Beginning in November 1999, the United Kingdom spearheaded the vaccination with a of all British children less than 20 years of age with a Neisseria meningitidis Serogroup C capsular polysaccharide–carrier protein conjugated vaccine. U.K. adolescents had had the greatest mortality rate from invasive meningococcal serogroup C disease, and so it is greatly reassuring that the number of deaths in the 15- to 17-year-old age group has dropped from 144 in the epidemiological year 1998 / 1999 to 11 in 2000 / 2001.

   Streptococcus pneumoniae vaccination was introduced into the childhood vaccination schedule of the USA following the strongly encouraging results of a randomized, double-masked, controlled trial in over 20,000 children less than 2 years of age. The seven Streptococcus pneumoniae serotypes targeted by the vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) are responsible for the majority of invasive pneumococcal disease in infancy, and the vaccine proved to have a serotype-specific efficacy of 97.7%. The vaccine serotypes also cover most of the penicillin-resistant and multiple-antibiotic resistant strains responsible for pneumococcal invasive disease during the first years of life. Other large clinical trials of this vaccine demonstrated an efficacy of between 33 and 73% against X-ray diagnosed pneumonia and of at least 34% against culture-proven S. pneumonia otitis media. Considering that the rate of invasive pneumococcal disease in European children (< 2 years old) appears to be about 25 to 50 cases per 100,000 per year, and that pneumococcal meningitis rates are about 10 cases per 100,000 per year, many European health authorities are now debating the inclusion of Streptococcus pneumoniae vaccination to their childhood immunization schedules.