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The effects of humoral, cellular and non-specific immunity on intracerebral Bordetella pertussis infections in mice
- Jean M. Dolby, D. E. Dolby, Caroline J. Bronne-Shanbury
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- Journal:
- Journal of Hygiene / Volume 74 / Issue 1 / February 1975
- Published online by Cambridge University Press:
- 15 May 2009, pp. 85-102
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When mice were injected intracerebrally with doses of Bordetella pertussis vaccine greater than 5 ImD50 and challenged intracerebrally 14 days later with virulent B. pertussis there was an immediate reduction in the numbers of organisms. An analysis of this in vivo bactericidal effect has shown that large doses of an unrelated vaccine, Salmonella typhosa, equivalent in cell mass to about 50 ImD 50 of B. pertussis vaccine can achieve this effect, so for such doses the effect must be partly non-specific. This action is not maintained and so is not ultimately protective. Local immunoglobulin was also demonstrable 14 days after 300 ImD 50 of B. pertussis vaccine but following smaller doses of 10–20 ImD 50 it could not be found until after the mice had been infected and the blood–brain barrier impaired.
A similar immediate reduction in the numbers of infecting organisms inoculated 1 day after vaccination has been shown to follow very small, non-protective doses of vaccines unrelated to B. pertussis and to be achieved with lipopolysaccharide and endotoxin isolated from B. pertussis. Brains were not sterilized and only in mice receiving protective B. pertussis vaccine was the lowering of infection maintained beyond 2 days and the brains eventually sterilized.
The antibody passively protecting mice against intracerebral infection was found in the 19 S and 11 S globulin fractions of the serum of once-vaccinated mice and in the 11 S and 7 S fractions of the serum of rabbits and ascitic fluid of mice receiving repeated doses of vaccine. The IgM probably eliminated infections by immediate sterilization but had to be present locally to do so since it was unable to pass from the circulation into the brain, and was therefore inactive when injected intraperitoneally. The IgA and IgG were not so restricted and both the 11 S and 7 S globulins were capable of exerting an immediate suppressive effect on infecting organisms. The 7 S globulin was also capable of a maintained or delayed suppressive effect.
Lymphocytes from fully protected once-vaccinated mice, transferred 2–3 weeks after intraperitoneal vaccination, were able to confer some protection when injected intraperitoneally or intracerebrally into recipient mice infected 2 weeks after transfer. Homologous, non-concentrated antiserum from once-vaccinated mice, injected intraperitoneally 1 hr. before infection sometimes augmented the transferred immunity, whereas alone it was inactive.
The effect of the antigen which elicits the bactericidal antibody and of the mouse-protective antiǵen on the growth of Bordetella pertussis in the mouse brain
- Jean M. Dolby, J. P. Ackers, D. E. Dolby
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- Journal:
- Journal of Hygiene / Volume 74 / Issue 1 / February 1975
- Published online by Cambridge University Press:
- 15 May 2009, pp. 71-83
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- Article
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- You have access Access
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The effect of antigens of Bordetella pertussis and their antibodies on brain infections by B. pertussis in mice are suppression of an infection immediately, so that the initial 90 % loss due to leakage from the brain is maintained or the numbers of bacteria are reduced even further, sometimes with complete sterilization particularly after a small lethal challenge of 10 LD 50 (mechanism 1), and a delayed antibacterial activity in vivo which does not begin until 3 days after challenge (mechanism 2). The first, immediate reaction is over in 2–3 days; the second is maintained from 3–4 days onwards, and results in elimination of the bacteria and protection of mice.
The parts played in vivo in overcoming infection in these two ways by two antigens and their respective antibodies have been investigated. These antigens are a lipopolysaccharide capable of eliciting an antibody which is bactericidal in vitro in the presence of complement called the ‘bactericidal antigen’, and the mouse protective antigen.
Considering first passive immunity, bactericidal antibody elicited by isolated antigen, and of high titre in vitro, is only very weakly active by mechanism (1) in vivo. Brains are seldom sterilized and mice not therefore protected. Antisera to whole cell vaccines whether they contain the ‘bactericidal antigen’ or not, or the protective antigen or not can more easily reduce infections by mechanism (1), eliminating small lethal challenges in some mice which are protected. A passive, intracerebrally protective antibody (PIPA) different from other known antibodies, has been postulated to account for this. Antisera to whole cell vaccine which is protective as denned in the potency assay, can, in additon to this, protect mice by mechanism (2) not only against 10 LD 50 but also 100 LD 50 challenge, and is the only antibody which can do this.
These antibodies have been investigated by injecting them with the challenging organisms. The antibody effects described above are given by antisera stimulated by several injections and also by the concentrated serum immunoglobulins of once vaccinated mice. The antibody, which is bactericidal in vitro only, is in the 7 S globulin fraction of the serum of once vaccinated mice. The protective antibody capable of overcoming small and large challenges is in the 19 S and 11 S globulins. The antibody, PIPA, protecting against small lethal challenges only is in the fraction A2 containing mainly 11 S globulin.
In active immunization experiments the suppression of infection which immediately follows intracerebral vaccination, but which only lasts 2–3 days (mechanism 1), is not dependent on either ‘bactericidal’ or protective antigens but on a component present in all our whole cell vaccines. Vaccines which also had protective antigen eliminated the remaining infection at 4–6 days after challenge by mechanism (2).
As in passive immunity, only the protective antigen can completely overcome 100 LD 50. Suppression of a small, lethal, intracerebral infection given 14 days after intraperitoneal vaccination by mechanism (1) may however be correlated with protective antigen.