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

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Abstract
SUMMARY: The development of immunity in mice toBordetella pertussisinduced 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 (ImD50). Intracorebral vaccination induced higher antibody titres than vaccination by the other two routes. The survival of infected mice given 1–3 ImD50 doses of vaccine intracerebrally 14 days before, followed a pattern similar to that after intraperitoneal or intravenous vaccination with up to 10 ImD50 of vaccine: the numbers of organisms increased for 3 days and then declined. Injection of about four ImD50 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 intracorebrally 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.