Monoclonal anti-LPS inner core antibodies protect against experimental hematogenous Haemophilus influenzae type b meningitis

This study tested the protective activity of antibodies to the LPS core of Haemophilus influenzae (Borrelli et al., Infect. Immun. 1995; 63: 3683-92) in a hematogenous meningitis model. Meningitis was established by intraperi toneal inoculation of infant rats with H. influenzae type b (Hib). The seve rity of infection was determined by daily assessment of mortality, symptoms of disease and weight changes. Mortality occurred rapidly after infection with 10(5) cfu/rat and most animals died within 24 h. At a lower infection dose (10(4) cfu/rat) the vats survived, but developed symptoms of disease s uch as tremor, hypothermia, lethargy and anorexia within 12-72 h post chall enge. Surviving animals showed decreased weight gain. Bacteremia was detect ed by daily blood-cultures in 10/10 rats and cleared 6 days after inoculati on. The monoclonal anti-LPS antibody MAHI 3 was used in passive protection studies. MAHI 3 increased the survival in the high inoculum group (10(5) cf u/rat) from 10-17% in control animals to 60-90%. At the lower inoculum conc entration (10(4) cfu/rat) MAHI 3 treatment reduced the symptoms and blood c ounts. Intraperitoneal injection of MAHI 3 was more effective than intranas al injection as shown by the effect on bacteremia. We conclude that anti-LP S antibodies can protect against mortality caused by hematogenous Hib infec tions in infant rats. (C) 2000 Academic Press.