The influence of molecular adjuvants in the cutaneous response to antigen after topical vaccination

A micro-emulsion (ME), previously shown to enable topical delivery of therapeutic amounts of protein, was used for immunisation of multiple strains of mice with tetanus toxoid (TT). Topical vaccination with TT alone induced low levels of serum antibody in the BALB/c and A/J strains, with C57Bl/6 the only strain capable of a significant TT-specific antibody response. Topical vaccination with TT in combination with murabutide and monophosphoryl lipid A adjuvant generated high humoral and cellular responses in both C57Bl/6 and the non-responsive strain, BALB/c, comparable to intramuscular injection with TT adsorbed to Alum adjuvant. High level immunity after topical administration with chemical adjuvants suggested that the poor response to TT alone in some strains was not due to a low bioavailability of protein. Weak immunity with TT alone may instead be related to passive absorption of antigen into skin that did not result in detectable inflammation or tissue damage. Immune mice given a booster vaccination also showed weak responses to topical TT alone; a further indication that the adaptive response to cutaneous antigen was highly dependent on adequate induction of innate immunity within local tissue. Our data supported the potential for high level adaptive immunity after cutaneous immunisation but only when combined with potent activators of the innate immune system.