Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus

Abstract

The adjuvant activity of Bordetella pertussis was investigated, both at the cellular and humoral levels, when the bacterial adjuvant was administered at various times before the primary antigenic stimulus of both 8 X 106 and 4 X 108 sheep erythrocytes. In all experiments, both adjuvant and erythrocyte antigen were given intraperitoneally. Adjuvant activity was measured on the basis of the primary immune response and on the degree of priming for the secondary immune reaction. A maximal effect on the primary immune response was found in mice which had received B. pertussis vaccine simultaneously with the erythrocyte antigen. A significant degree of adjuvancy was also demonstrable when B. pertussis vaccine was administered within a period of 48 hr before antigen. Adjuvant effectiveness was less as the time interval between the injection of antigen and adjuvant increased. The process of priming for the secondary response, however, was found to be equally affected when the adjuvant was given either simultaneously with the antigen or 12, 24, and 48 hr before sheep erythrocytes. On the basis of these and previous findings, it is suggested that adjuvancy of B. pertussis is caused chiefly by additional recruitment of responding cells. It is also suggested that memory-cell production may develop concurrently with, but independently of, the cellular proliferative events which lead to antibody formation during the primary immune response. Central Institute for Laboratory Animals in Hannover, Germany. Antigen. Primary immunizations were performed with either 8 X 106 or 4 X 108 sheep erythrocytes(SE), each dose suspended in 0.2 ml of phosphate-buffered saline (PBS), pH 7.2. Secondary immunization con-590

Variables which affect suppression of the immune response induced by Pseudomonas aeruginosa exotoxin A

“…Concanavalin A, a plant lectin and T-cell mitogen, has been shown to result in immunosuppression when administered before or during antigenic stimulation but results in enhancement when administered after the antigen (5,30). Similar effects have been observed with interferon (2), Bordetella pertussis vaccine (6), Mycobacterium bovis BCG (31), and cholera enterotoxin (13,16). This study suggests that timing of administration of exotoxin A determines the immunomodulatory effect of the toxin.…”

“…Tubercle bacilli have been observed to elicit an immunoenhancing effect when administered with the antigen (7) but to induce suppression of the response when given before the antigen (31). A similar effect has also been observed for cholera toxin (13,16) and Bordetella pertussis vaccine (6). We now report that timing of exotoxin A administration relative to antigenic stimulation can have a dramatic effect on the ability of the toxin to modify the immune response.…”

“…The ability of bacterial products to alter the immune response is well documented. A number of bacterial cell wall products as well as material isolated from culture supernatants have been shown to have an immunoenhancing effect (1,7,27), and conversely, other products isolated from bacteria have been shown to suppress the response of immune cells to antigenic stimulation (6,31). Bacterial toxins have been observed to modulate the immnune response.…”

“…Molten agarose in Eagle minimal essential medium was mixed with washed SRBCs or TNP-coupled SRBC target cells (24) and the appropriate spleen cell suspension. The mixture was poured onto microscope slides, allowed to gel, and incubated in a humidified chamber at 370C for 1.5 h. The slides were flooded with guinea pig complement that had been previ-penoa ana appearea 1o ennance me response on aays ) ana 6.…”

Suppression of the immune response by microorganisms.

“…The vaccine made from this organism has been shown to influence immune response in several experimental models. Finger and co-workers have carefully defined some of the variables in a series of papers (32)(33)(34). They confirmed the potent adjuvant effect of killed B. pertussis on antibody response to SRBC.…”