Local and Systemic Immune Responses to Intratracheal Instillation of Antigen and DNA Vaccines in Mice

Abstract

Purpose. The purpose of this study was to determine the immunization 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 intratracheally 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 intratracheal 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 immunization, 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 promising alternative to conventional vaccination by injection.

Particle Size Influences the Immune Response Produced by Hepatitis B Vaccine Formulated in Inhalable Particles

“…Although published studies, including ours (13), suggest that the mucosal route of administration, including nasal, pulmonary and vaginal routes, are a viable non-invasive alternative for delivering HBsAg antigen (44)(45)(46)(47), no studies have specifically investigated the role of particle size in generation of immune response upon inhalational delivery. This manuscript is the first to investigate the effect of particle size on the uptake by rat alveolar macrophages and relate the sizedependent uptake to in-vivo immune response.…”

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

“…The only other methodology reported for direct delivery of dry powders is tracheostomy (Lombry et al, 2004;Wong, 2007;Fernandes and Vanbever, 2009). This method involves a surgical incision to expose the trachea and the placement of powders into a cannula that is inserted towards the lung or directly into the upper respiratory tract.…”

CpG oligodeoxynucleotides as DNA adjuvants in vertebrates and their applications in immunotherapy

“…Even though many investigators reported the possible side-effects of inducing local inflammation by CpG ODN, recent evidence has shown that DNA vaccines with CpG ODN as an adjuvant delivered to the lung does not induce any local signs of inflammation [63]. This finding implies that the increased number and unmethylated status of CpG motifs, particularly when present in a particular base context, may be identified as a 'foreign' molecular pattern and thus activate appropriate immune responses.…”

“…This finding implies that the increased number and unmethylated status of CpG motifs, particularly when present in a particular base context, may be identified as a 'foreign' molecular pattern and thus activate appropriate immune responses. Fortunately, no direct evidence that bacterially-derived DNA causes clinically significant damage has yet been reported [63].…”