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
Mucosal delivery of inactivated vaccines that are able to elicit protective immune responses against respiratory diseases has been a long time goal of vaccinologists. Such vaccines would enable a more appropriate means of vaccination against respiratory diseases than those currently delivered by a parenteral route. The intranasal delivery of inactivated influenza vaccine plus the ISCOMATRIX (IMX) adjuvant, simply mixed together, was able to induce serum haemagglutination inhibition (HAI) titres in mice far superior to those obtained with unadjuvanted vaccine delivered subcutaneously. Furthermore, the IMX adjuvanted vaccine delivered intranasally induced mucosal IgA responses in the lung, nasal passages and large intestine, together with high levels of serum IgA. Intranasal delivery of IMX adjuvanted influenza vaccine in sheep gave antibody responses in both serum and nasal secretions that surpassed the levels obtained with unadjuvanted vaccine administered subcutaneously. These observations suggest that it may be possible to induce effective immunity to influenza in humans by intranasal vaccination with an IMX adjuvanted inactivated vaccine.
