The intracerebral infection of mice with Bordetella pertussis

Abstract

The growth of virulent strains of Bordetella pertussis in the brains of mice was studied by carrying out viable counts on mice killed at various times during the infection. The results suggested that this system conformed to the general model which postulates that the organisms causing death multiply in vivo at a rate which is constant for all doses and that death is certain to occur when the number of organisms reaches a certain constant figure.Perhaps the most important factor in this route of infection is the lodgement of the parasite in the host, for if this is accomplished a single organism grows until the lethal level is reached. There is no sublethal infection.In actively and passively protected mice, the growth of the organism is approximately the same as in unprotected controls for the first 4–5 days. At this time there is a striking change in protected animals and the viable count falls rapidly and progressively and the animals survive. At the same time the blood-brain barrier becomes permeable and circulating antibodies diffuse into the brain. In vitro, specific antisera plus complement are highly bactericidal.

An immunofluorescence study of the action of antibody in experimental intracerebral infection of mice with Bordetella pertussis

“…An increase in the permeability of the barrier after infection with B. pertussis was demonstrated by Berenbaum et al (1960) in experiments with radio-iodinated albumin and by Holt et al (1961) in experiments with human serum or a dye. Our results show that there is a break in the blood-brain barrier 3 or 4 days after the start of the infection and they provide an explanation for the findings of Dolby and Standfast (1961), Standfast and Dolby (1961) and Iida et al (1963) that, for a certain period before they gradually disappear, the pertussis organisms multiply in brains of passively immunised mice at nearly the same rate as they do in the brains of untreated animals. The underlying mechanism involved in increased permeability is still obscure.…”

The effect of the antigen which elicits the bactericidal antibody and of the mouse-protective antiǵen on the growth ofBordetella pertussisin the mouse brain

“…This assay consists of injecting mice once intraperitoneally with a suitable dose of vaccine and challenging them intracerebrally 14 days later with 100 LD50 of a highly mouse-virulent strain of Bordetella pertussis organisms. The protection of mice by this method, and also the passive protection of mice following the intraperitoneal injection of antisera against the usual size of intracerebral challenge, have been shown to depend not on the immediate sterilization of the brain but on an in vivo bactericidal effect which becomes evident 3-4 days after challenge (Berenbaum, Ungar & Stevens, 1960;Dolby & Standfast, 1961). …”

Intracerebral mouse protection test for pertussis vaccine. II. Immunosuppression with cyclophosphamide

“…But this argument is weakened by their use of a passive immunization test to detect the formation of antibodies. This may be an ineffective test system because of the short half-life of mouse immunoglobulins (9) in relation to the 5-day interval between challenge and the breakdown of the blood-brain barrier (6). The fourth argument, that early immunity was not associated with the appearance of agglutinating or complement-fixing antibodies, is not strong since Evans and Perkins themselves showed that certain vaccines, such Can.…”

“…In 1961 Dolby and Standfast (6) showed that the critical events following intracerebral challenge of mice with B. pertussis occur about 5 to 7 days after the challenge. Until that time, B. pertussis injected into the brains of vaccinated mice grows at the same rate as in unvaccinated animals.…”