Studies on respiratory immunization with tetanus toxoid: The role of adjuvants

Abstract

SUMMARYAerosol vaccination of mice with purified plain tetanus toxoid does not induce an immune response unless a suitable adjuvant is added.Aluminium phosphate is without effect by aerosol treatment. Killed cells of Klebsiella pneumoniae, although effective, are unsatisfactory owing to the long inhalation period needed.Killed Bordetella perussis cells were found to be an excellent adjuvant. A single aerosol treatment with a toxoid-B. pertussis mixture during a moderate exposure period evoked a considerable immune response. With repeated aerosol treatment of primed mice the addition of adjuvant is not required; booster treatment with plain toxoid is at least as effective.Extracts from B. pertussi8 cells exert as good an adjuvant effect as the wholecell vaccine. The remaining cell-wall debris also appears to be an active adjuvant.In combination with constant doses of adjuvant (108 B. pertussi8 cells), the 50 % protective doses (ED 50) of toxoid were determined by inhalation and by s.c. injection and were found to be 041875 and 0-0625 LFU respectively. This would imply that, as a result of the adjuvant action, the s.c. ED 50 is reduced by approximately a factor of 20; whereas the respiratory ED 50 is decreased by at least a factor of 100.It is suggested that the much more pronounced adjuvant activity in aerosol immunization is associated with the induction of strong cell-mediated hypersensitivity in the respiratory tract.

Influence of Detergent on Aerosol Allergic Sensitization with Enzymes of <i>Bacillus subtilis</i>

“…Such an interaction could lead to anti gen aggregation with better presentation to immunocompetent cells. It has been suggested that Bordetella pertussis may exert adjuvant effect in the respiratory tract by stimulating a local inflammatory reaction rich in T lymphocytes with subsequent enhancement of cell-mediated immunity [2]. Such a specific cell-mediated response does not appear to play a role in the adjuvant effect of SDBS.…”

“…This effect is observable upon secondary challenge. (2) Trypsin has been reported to be a B-cell mitogen with its mitogenicity dependent upon enzymatic activity [37], (3) It has been suggested that proteases may expose potassium binding sites on cells and thus activate the cation pump, a necessary function for stimulation of lymphocytes by mitogens and antigens [18]. (4) Proteases are potent activators of com plement and can generate split products of C3 and C5 [14,39].…”

Progress toward development of an inhalation vaccine against botulinum toxin

“…One further observation has been that, whereas a single nasal administration of TeNT produces no detectable serologic response, a primary nasal immunization causes an increase in the antigen-specific serum IgA1 response to a subsequent parenteral administration [40]. When taken in the aggregate, the laboratory animal and human studies suggest that intranasal vaccination with TeNT does not evoke a significant mucosal or systemic immune response, however, intranasal vaccination can be as effective as parenteral vaccination when administered as a priming or booster immunization.…”

Aerosolimpfung von Mäusen mit inaktiviertem Influenzavirus

“…Alexander, 1973;Hofstad, 1967; Jemski u. Walker, 1976;Scott u. Sydiskis, 1976 Bartlema (1966) und Bartlema et al (1972) in Verbindung mit Toxoidimpfstoffen beschrieben worden ist.…”