Local and systemic immune responses to intratracheal instillation of antigen and DNA vaccines in mice

Purpose. The purpose of this study was to determine the immuniza-tion efficacy of antigen and DNA vaccines after delivery to the lung, to assess the integrity of the pulmonary tissue after vaccination, and to elucidate mechanisms involved in the induction of immunity. Methods. Ovalbumin, the plasmid encoding ovalbumin, the hepatitis B surface antigen (HBsAg), or plasmid encoding HBsAg were intra-tracheally instilled or injected in quadriceps in mice. The immune response and its Th polarization were analyzed over time. Markers of inflammation were measured in bronchoalveolar lavage, and lung histology was performed. The fate of ovalbumin following intratra-cheal instillation was studied. Results. According to the vaccine, the pulmonary route produced stronger or equivalent humoral and cellular responses systemically and locally in the lung as compared to injection. The IgG subclasses and cytokine pattern indicate that the immunity was preferentially polarized toward the Th2 and Th1 type for antigen and DNA immu-nization, respectively. Ovalbumin penetrated the respiratory tissue and blood poorly after intratracheal instillation, suggesting that the immune response was triggered at airway surfaces. Overall, vaccines delivered to the lung did not induce any local sign of inflammation. Conclusions. Pulmonary administration of vaccines might be a prom-ising alternative to conventional vaccination by injection. KEY WORDS: antigens and DNA vaccines; fate of vaccine mol-ecule; IgG; intratracheal instillation; lungs, proliferation assay