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

Aerosol 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. pertussis cells exert as good an adjuvant effect as the whole-cell vaccine. The remaining cell-wall debris also appears to be an active adjuvant.In combination with constant doses of adjuvant (10(8)B. pertussis cells), the 50% protective doses (ED 50) of toxoid were determined by inhalation and by s.c. injection and were found to be 0.1875 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.