ABSTRACT
A key barrier to producing effective nasal immunisations is the low efficiency of uptake of vaccines across the nasal mucosa. Using a recently developed cannulation system, we examined the antibody response induced by nasal immunisation with an ISCOMATRIX influenza vaccine. This showed for the first time, that following nasal vaccination, specific antibodies enter the circulation of primed animals via the draining lymphatics as a wave that peaks approximately 5-6 days after vaccination. These antibodies included some of the IgA isotype and possessed functional haemagglutination inhibition activity. These responses, though small, were induced using a very simple delivery system, emphasising the applicability of this cannulation model for evaluation of excipients and adjuvants aimed at improving intranasal vaccine efficacy.
Subject(s)
Adjuvants, Immunologic , Cholesterol/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Phospholipids/immunology , Saponins/immunology , Adjuvants, Immunologic/administration & dosage , Administration, Intranasal , Animals , Antibodies, Viral/analysis , Cell Proliferation , Cholesterol/administration & dosage , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Hemagglutination Inhibition Tests , Immunization, Secondary , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Influenza Vaccines/administration & dosage , Lymph/immunology , Lymphocytes/immunology , Models, Animal , Phospholipids/administration & dosage , Saponins/administration & dosage , SheepABSTRACT
We have developed and validated a novel model to investigate the efficacy of nasal vaccine delivery. Based on lymphatic cannulation of the tracheal lymph trunk of sheep, the model allows collection of lymph draining from the Nasal Associated Lymphoid Tissue. The model is suitable for determining both the amount of material that is absorbed into the lymphatic system, following intra-nasal delivery and the immune response that occurs following vaccination into the nasal area. The cell populations that track in this duct were phenotyped and found to be similar to those previously reported to be present in efferent lymph draining from peripheral lymph nodes. Following intra-nasal spray, we demonstrated that the amount of material recovered in draining lymph is only a very small fraction of the total delivered. Nevertheless, intra-nasal spraying of a vaccine could activate local immune cells. The method described will be invaluable for optimising intra-nasal delivery systems by allowing a separate optimisation of vaccine uptake and immune responses induction.
