The effect of the antigen which elicits the bactericidal antibody and of the mouse-protective antigen on the growth of Bordetella pertussis in the mouse brain.

ABSTRACT

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 defined in the potency assay, can, in addition 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 A(2) 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.