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A vaccine was first developed in the United States by the Armed Services shortly after chick embryo virus cultures were successfully employed in 1940. The first vaccine was commercially available in 1945.

In France, the first influenza vaccine dates back to 1953. Since that time influenza vaccines have undergone constant improvement.  

Between 1920 and 1930, Margaret Pittman serologically characterized six distinct serotypes (a - f) which make up the capsulated strains of H. influenzae. She observed that the b strain was found in large concentrations in the cerebrospinal fluid and blood of young children afflicted with meningitis. She also showed that serum antibodies conferred b type-specific protection from infection in animal experimentation.

In 1933, Fothergil and Wright showed that various serums, and almost all adult serums, had a "bactericidal power" vis-à-vis Hib and that an inverse relation existed between the incidence of Hib meningitis and this bactericidal activity. They also showed that Hib meningitis primarily affects children under the age of 5 years. Later it was discovered that it is the polysaccharide or polyribosyl ribitol phosphate (PRP) within the capsule of type b that is immunogenic. The PRP was subsequently purified to obtain a vaccine that has gained wide usage in Finland and in the USA (North Carolina) since 1974.

These studies led to the first Hib polysaccharide vaccine which was licensed in April 1985 in the United States for preschool children between the ages of 24 to 59 months. This vaccine, based on PRP, was entirely ineffective before the age of 18 months. This posed a major difficulty for routine immunization because epidemiological data indicated a clear necessity to protect infants before their sixth month.

The limitations of capsular polysaccharide (CP) were finally overcome when Schneerson and Robbins attached PRP to diphtheria toxoids thereby producing the first polysaccharide conjugate vaccine. The vaccine was more immunogenic and more effective than the previous and was licensed for commercial use in 1987 for children 18 months and older. Though younger children were still at risk, three new vaccines were developed shortly thereafter using as conjugating agent a nontoxic protein derived from a mutant strain of D. diphteriae, an outer membrane protein complex of Neisseria meningitidis, or even a tetanus toxoid. These new conjugated vaccines were found to be very immunogenic in infants and children. They can be administered to children as young as three months of age.