Staphylococcal enterotoxin B (SEB) toxoid-containing microspheres were tested for efficacy in rhesus monkeys as a vaccine candidate for respiratory SEB toxicosis and toxic shock. Forty monkeys were randomly separated into 10 groups of four monkeys each: 9 groups were vaccinated with the microspheres via combinations of mucosal and nonmucosal routes, and 1 group served as nonvaccinated controls. Both vaccinated and nonvaccinated monkeys were then challenged with a high lethal dose of SEB aerosol. Monkeys primed with an intramuscular dose of the microspheres followed by an intratracheal booster all survived the SEB challenge. Overall, monkeys with an intratracheal booster generally had the highest antibody levels, which is consistent with their high survival rate and lower rate of illness. Protective immunity was correlated with antibody levels in both the circulation and the respiratory tract. The protection was not due to the depletion or anergy of SEB-reactive T cells, since SEB-induced proliferation in cultures of circulating lymphocytes was not significantly reduced after the microsphere vaccination. It is evident that the nonsurvivors did not die of systemic anaphylaxis or hypersensitivity because the monkeys did not die immediately after SEB challenge and there were no significant differences in histamine levels between the vaccinated and control monkeys before and after SEB challenge. The antibodies seemed to neutralize the SEB that got into the airway and the circulation.

Rhesus monkeys immunized intramuscularly or orally with staphylococcal enterotoxin B (SEB) toxoid or SEB toxoid incorporated in microspheres made of poly(DL-lactide-co-glycolide) were challenged with a lethal dose of aerosolized SEB to study their immunity and cellular responses in the circulation. It was found that circulating antibodies play a critical role in preventing SEB from triggering toxicosis. Monkeys with high levels of antibodies survived, while those with low levels underwent 2 to 3 days of toxicosis and died. Intramuscular immunization induced high levels and oral immunization induced low levels of antibodies. The circulating antibodies in surviving monkeys decreased dramatically within 20 min and started to rebound at 90 min after SEB challenge. At 90 min, the dying monkeys showed in the circulation a dramatic increase of polymorphonuclear leukocytes and decreases of NK cells and monocytes (CD16 and CD56 markers) as well as of lymphocytes with HLA-DR, CD2, CD8, and IL2Ra (CD25) markers. The number of polymorphonuclear leukocytes showed an inverse correlation with the numbers of monocytes and various lymphocyte subpopulations which, except for IL-2R, CD16, and CD56(+) cells, showed a direct correlation with one another. The changes in the populations of leukocytes, monocytes, NK cells, and lymphocytes seem to be an indication of initial toxicosis; however, the roles of these cells in toxicosis and death remain to be defined.Staphylococcal enterotoxin B (SEB) causes food poisoning when ingested and toxic shock when it enters the blood circulation and affects systemic tissues (3,6,10,16,19,39,44). The pathological mechanisms of toxicosis and death are still largely unknown. SEB, a superantigen, binds to class II histocompatibility antigens on antigen-presenting cells, and the SEB-class II antigen complex is then presented to and activates T cells bearing certain T-cell antigen receptor V,B elements (11,22). It has been suggested that activation of both the antigen-presenting cells and T cells results in the production of large amounts of monokines and lymphokines, which cause the disease (21,26). On the other hand, other cell types may also be involved. Scheuber and coworkers (37, 38) have shown that SEB injected intradermally into cynomolgus monkeys results in an immediate-type skin hypersensitivity reaction which is caused mostly by degranulation of mast cells. This mast cell degranulation may be caused by a direct activation by SEB of mast cells or of nerve cells which release neuropeptides, which then activate mast cells (1). Histamine H2 receptor antagonists can block SEB-induced emesis and skin reactions (37). Recently, we have also shown that SEB can induce serotonin release from cultured mast cells (23).If SEB intoxication is caused by activated macrophages, T cells, and other cell types and their mediators, the toxicosis could be a cascade and/or a combination of sequential pathophysiological changes among functionally interrelated tissues. A blockade of the initial phase in which SEB reacts ...