Polyvalent vaccines of killed whole pneumococcal cells were developed in the second decade of the twentieth century to prevent epidemic pneumococcal pneumonia in industrial populations, and they were shown to be safe. Demonstration of their efficacy remained uncertain, however, because of the design of trials employed for that purpose. Vaccines of purified capsular polysaccharides, introduced in the 1930s, were shown unequivocally to protect against infection with the types represented in them in the 1940s. In addition, the vaccine was shown to reduce by about half the likelihood of colonization of the upper respiratory tract with pneumococcal types represented in the vaccine. Vaccination had no demonstrable effect on previously established carriage of a type represented in the vaccine.

Vaccines composed of the purified polysaccharides of pneumococcal types responsible for the majority of pediatric infections have proved to be poorly immunogenic and to provide little or no protection against infection. Similar vaccines for the prevention of infection with H. influenzae and N. meningitidis group C also have been ineffective.

More details of the limitations of existing vaccines can be found in the recent review by Austrian (1984).

Streptococcus pneumoniae is a gram-positive capsulated coccus found commonly in pairs and is a normal inhabitant of the human upper respiratory tract. More than 80 capsular serotypes are known, each distinguished by the unique polysaccharide structure of its capsule. All serotypes are not equally invasive; about 90 percent of bacteremic infections are caused by 23 serotypes. The frequency with which different pneumococcal serotypes cause infection in infants and young children and in adults differs. In the pediatric population, pneumococcal types 6A, 6B, 14, 19F, 19A, and 23F account for more than half of all pneumococcal infections. In adults, types 1, 3, 4, 7F, 8, and 12F are seen more commonly. The currently licensed vaccine, which contains 23 capsular polysaccharides, includes antigens from types found at all ages. The chemical compositions of many of the polysaccharides in the U.S.-licensed vaccine are known.

In the normal human host, defense against invasion of internal bodily sites by pneumococci depends primarily on type-specific serum antibodies to pneumococcal capsular polysaccharides. This conclusion is based on epidemiologic studies of pneumococcal infections in man, on experiments in a variety of susceptible animal species, and on the therapeutic effect of type-specific anticapsular antiserum in the treatment of pneumococcal pneumonia prior to the advent of sulfonamides and antibiotics. In addition, previous trials in adults of vaccines of