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

Blake, Hezekiah; Wardlaw, A. C.

doi:10.1139/m69-246

Cited by 2 publications

(4 citation statements)

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“…There was only a little protection of TF 1 mice against a 50,000 challenge, with antiserum either intraperitoneally or intracerebrally. Blake & Wardlaw (1969) showed that the immunosuppressive reagent, cyclophosphamide, inhibited both active and passive protection of mice by vaccine or 715 JEAN M. DOLBY intraperitoneal serum against a 50,000 challenge. In one experiment by my colleague, Dr J. P. Ackers, cyclophosphamide-treated TO mice given intraperitoneal antiserum were protected only to the same degree as TF 1 mice.…”

Section: Resultsmentioning

confidence: 99%

“…The role of antibody in the active protection test is, however, controversial and the possibilities have been set out by Blake & Wardlaw (1969). The inability to protect passively mice that do not immunize supports their experiments, suggesting that protection of mice by pertussis antiserum may not be such a passive phenomenon as is generally thought.…”

Section: Discussionmentioning

confidence: 99%

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Passive protection of mice against intracerebral infections with Bordetella pertussis

Dolby

1972

Epidemiol. Infect.

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SUMMARYThe passive protection of mice against an intracerebral infection with Bordetella pertussis, by antiserum introduced directly into the brain with the infecting organisms, was compared with the protection afforded by intraperitoneal antiserum. The antibody effective by the intracerebral route is that which is adsorbed onto the infecting organisms, although it does not affect the viability of the organisms in vitro in the absence of complement.Passive protection against organisms introduced intracerebrally takes place in one of two ways, depending on the size of the challenge: (1) after 3-4 days' growth, the growth rate declines so that the number of organisms does not reach the figure lethal for the mouse; (2) the organisms do not appear to multiply, as their numbers decline from the moment of injection, so that the brain is sterile after 2 days.Many of the mice protected against a challenge of 50,000 organisms (ca. 100 LD 50) by intraperitoneal or intracerebral antiserum recover by the first mechanism. The second mechanism operates after a smaller challenge of 5000 organisms (ca. 10 LD 50), irrespective of whether the antiserum is given intracerebrally with the challenge, or intraperitoneally within several hours of challenge. Too much antiserum given intracerebrally with a 50,000 challenge, but not with a 5000 challenge, inhibits protection.In some mice, virulent antibody-treated organisms which have not been killed, grow very slowly over a long period, but are eventually eliminated from the brain.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Passive protection of mice against intracerebral infections with Bordetella pertussis

Dolby

1972

Epidemiol. Infect.

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“…7 and 8). The experiments of Blake & Wardlaw (1969) raise the question whether anything other than antibody is involved.…”

Section: Discussionmentioning

confidence: 99%

“…Evans & Perkins suggested that two types of immunity were operative in the mouse potency assay of vaccine. Blake & Wardlaw (1969), however, quote an experiment of Dr Fischel's in which this short-lived immunity was abolished after body irradiation and have shown that the immunity present one day and 14 days after vaccination IP is inhibited by the immuno-suppressive drug, cyclophosphamide.…”

Section: Introductionmentioning

confidence: 99%

The influence of the route of immunization on the protection of mice infected intracerebrally withBordetella pertussis

Standfast

Dolby

1972

J. Hyg.

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The development of immunity in mice to Bordetella pertussis induced by intracerebral, intravenous or intraperitoneal vaccination was analysed in terms of the viable bacteria in the brain after intracerebral challenge, the serum antibodies, and protection against the sublethal infection of the lung that follows intranasal inoculation.A vaccine introduced intracerebrally was five to ten times more effective than that given intraperitoneally or intravenously, as measured for each route by the amount of vaccine required to protect half the mice against an intracerebral challenge 14 days later (ImD 50). Intracerebral vaccination induced higher antibody titres than vaccination by the other two routes. The survival of infected mice given 1-3 ImD 50 doses of vaccine intracerebrally 14 days before, followed a pattern similar to that after intraperitoneal or intravenous vaccination with up to 10 ImD 50 of vaccine: the numbers of organisms increased for 3 days and then declined. Injection of about four ImD 50 of vaccine intracerebrally produced a local immunity, resulting in an immediate kill of challenge organisms given 14 days later. Such an effect following intraperitoneal vaccination was achieved only against challenges with an avirulent strain. It is suggested that better stimulation of circulating antibody and local immunity in the brain together account for the better protection induced by intracerebral vaccine.Immunity to an intracerebral infection appears therefore to have at least three components, each specific for pertussis. The first, like that induced by intraperitoneal and intravenous vaccination, reaches a maximum in 2 or 3 weeks and is probably an expression of a general response by the animal operating not earlier than 3 days after infection. The second is a local immunity, appearing after the same interval. The third is a short-lived local immunity which has been described by previous workers; it immediately follows the injection intracerebrally of ten times less vaccine than that needed to protect against a challenge 14 days later and lasts only 2-3 days. The second and third types result in immediate sterilization of the infection.Mice recovering from sublethal brain infection with avirulent organisms were immune to a second infection with a virulent organism, but this was achieved not by the ability to kill the re-infecting organisms immediately on injection into the brain, but only after the 3-4 days lag such as follows intraperitoneal vaccination.

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

Cited by 2 publications

References 10 publications

Passive protection of mice against intracerebral infections with Bordetella pertussis

Passive protection of mice against intracerebral infections with Bordetella pertussis

The influence of the route of immunization on the protection of mice infected intracerebrally withBordetella pertussis

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