Efficacy of Human Hyperimmune Globulin in Prevention of Haemophilus influenzae Type b Disease in Infant Rats

Abstract
To determine the protective efficacy of human hyperimmune globulin to H. influenzae type b disease in an infant rat model, hyperimmune globulin containing 600 .mu.g of anti-polyribophosphate (PRP) antibody per ml was compared to conventional immune globulin containing 66 .mu.g 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 1st-order disappearance curve during the first 7 days. The initial half-life (t1/2) for anti-PRP antibody was 2.38 days in rats nasally colonized but not detectably bacteremic with H. influenzae type b and significantly longer (t1/2, 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 iniital serum antibody levels and the levels during the 8-day observation period predicted protection. Rats maintaining serum antibody levels .gtoreq. 50 ng/ml to day 8 had a 10% bacteremia and 5% meningitis incidence in contrst with 95% bacteremia (P < 0.001) and 55% meningitis (P < 0.001) in rats with < 50 ng of anti-PRP antibody per ml. Thus, studies of the pharmacology and efficacy of hyperimmune globulin are warranted in high-risk children unable to respond to active immunization.