Mucosal immunoadjuvant activity of liposomes: induction of systemic IgG and secretory IgA responses in mice by intranasal immunization with an influenza subunit vaccine and coadministered liposomes.
This paper reports on a novel immunoadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum IgG response relative to the response to i.n. immunization with the antigen alone. In addition, the liposomal vaccine induced a secretory IgA (sIgA) response in the mucosa of the lungs and nasal cavity. Both serum IgG and sIgA responses persisted up to at least 21 weeks postimmunization. Immune stimulation was observed with negatively charged liposomes consisting of phosphatidylcholine (PC), cholesterol and dicetylphosphate (DCP), but not with zwitterionic liposomes, consisting of PC and cholesterol alone. Remarkably, for stimulation of serum IgG responses and induction of an sIgA response, liposomes could be simply mixed with the antigen. Moreover, i.n. administration of empty liposomes up to 48 h prior to i.n. immunization with the subunit antigen also resulted in immune stimulation, indicating that the liposomes did not exert their adjuvant effect by acting as a carrier for the antigen. The liposomal vaccine conferred protection against infection. It is concluded that liposomes, administered i.n., provide a promising adjuvant system for stimulation of antibody responses in general, and mucosal sIgA responses in particular.
de Haan
A
A
Department of Physiological Chemistry, Groningen Institute for Drug Studies, University of Groningen, The Netherlands.
Geerligs
H J
HJ
Huchshorn
J P
JP
van Scharrenburg
G J
GJ
Palache
A M
AM
Wilschut
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012137:Respiratory System / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008081:Liposomes