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 intraperitoneal inoculation of infant rats with H. influenzae type b (Hib). The severity 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 rats survived, but developed symptoms of disease such as tremor, hypothermia, lethargy and anorexia within 12-72 h post challenge. Surviving animals showed decreased weight gain. Bacteremia was detected by daily blood-cultures in 10/10 rats and cleared 6 days after inoculation. 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)cfu/rat) from 10-17% in control animals to 60-90%. At the lower inoculum concentration (10(4)cfu/rat) MAHI 3 treatment reduced the symptoms and blood counts. Intraperitoneal injection of MAHI 3 was more effective than intranasal injection as shown by the effect on bacteremia. We conclude that anti-LPS antibodies can protect against mortality caused by hematogenous Hib infections in infant rats.
Borrelli
S
S
Divisions of Clinical & Oral Bacteriology, Karolinska Institute, Huddinge, 86, S-141, Sweden.
Diab
A
A
Lindberg
A
A
Svanborg
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016470:Bacteremia / Q000517:prevention & control; D006193:Haemophilus influenzae / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008583:Meningitis, Haemophilus / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides