Adverse reactions and endotoxin content of polysaccharide vaccines.

Adverse reactions occurring when 1.5 million children and young adults were vaccinated with different lots of group A meningococcal and one lot of Haemophilus influenzae type b capsular polysaccharide vaccines were analyzed on the basis of records kept by local health personnel and 19,000 special questionnaires. The incidence of anaphylactic reactions was 0.8 per 100,000 injections. A pyrogen-like reaction--high fever appearing soon after injection and disappearing within six hours--was seen in 1.8% of children 3 months to 5 years old who received the meningococcal vaccine in the first vaccination project. This reaction was most common in children below three years. Its frequency varied with different vaccine lots and was found to be correlated with the endotoxin content of the vaccines estimated by either the limulus assay or by pyrogen test in rabbits. On the basis of these results we propose that capsular polysaccharide vaccines should pass the pyrogen test with a dose of one mug polysaccharide per kg of rabbit weight. With such vaccines, the incidence of high fever was reduced to 0.5% in children of the same age group.