Abstract
To determine the protective efficacy of human hyperimmune globulin to Haemophilus influenzae type b disease in an infant rat model, we compared hyperimmune globulin containing 600 μg of anti-polyribophosphate (PRP) antibody per ml to conventional immune globulin containing 66 μg of anti-PRP antibody per ml. The hyperimmune globulin was fractionated from the pooled plasma of 55 adult donors immunized with PRP, the capsular polysaccharide of H. influenzae type b. The disappearance of passively administered antibody was biphasic, with a linear first-order disappearance curve during the first 7 days. The initial half-life for anti-PRP antibody was 2.38 days in rats nasally colonized but not detectably bacteremic with H. influenzae type b and significantly longer (half-life, 10.3 days; P < 0.01) in noncolonized animals. Hyperimmune globulin afforded 10 times the protection of conventional globulin against bacteremia and meningitis. Globulin depleted of anti-PRP antibody offered no protection. The initial serum antibody levels and the levels during the 8-day observation period predicted protection. Rats maintaining serum antibody levels greater or equal to 50 ng/ml to day 8 had a 10% bacteremia and 5% meningitis incidence in contrast with 95% bacteremia (P < 0.001) and 55% meningitis (P < 0.001) in rats with less than 50 ng of anti-PRP antibody per ml. We conclude that studies of the pharmacology and efficacy of hyperimmune globulin are warranted in high-risk children unable to respond to active immunization.
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Selected References
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