Nasal and parenteral immunizations with diphtheria toxoid using monoglyceride/fatty acid lipid suspensions as adjuvants.
A novel suspension system was developed where monoglycerides were formulated together with fatty acids and subsequently admixed with antigens. In the present study, diphtheria toxoid was used as a model antigen primarily due to its weak immunological properties as well as to its importance as a future human vaccine for mucosal, particularly nasal immunization. The formulations were administered parenterally and/or nasally to mice whereafter the immune response was determined. In the present study, we have shown that mono-olein/oleic acid vesicles enhance the immunogenicity of admixed diphtheria toxoid in mice to the same level as Alum adsorbed (or Freund's complete adjuvant) when administered parenterally or nasally. It was also shown that the immunogenicity was linked to the length of the acyl chain of the lipids, where shorter acyl chains resulted in reduced titers. Furthermore, shorter acyl chains also gave rise to more pronounced toxic reactions at the injections sites, such as necrosis and alopeci, both of which were lacking when the optimal formulation consisting of mono-olein and oleic acid was used. Thus, this lipid matrix has in our view a great potential as an immunological adjuvant with an exceptionally simple and efficient preparation procedure without organic solvents and with low cost endogenous lipid based raw materials.
Schröder
U
U
Department of Veterinary Bacteriology, Swedish University of Agricultural Sciences, Uppsala. ulf.schroder@bmc.uu.se
Svenson
S B
SB
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D004168:Diphtheria Toxoid / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005227:Fatty Acids / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005989:Glycerides / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007279:Injections, Subcutaneous; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000473:pathology / Q000648:ultrastructure; D009500:Neutralization Tests; D009829:Oleic Acids / Q000008:administration & dosage / Q000276:immunology; D013535:Suspensions
D000276:Adjuvants, Immunologic; D004168:Diphtheria Toxoid; D005227:Fatty Acids; D005989:Glycerides; D007074:Immunoglobulin G; D008081:Liposomes; D009829:Oleic Acids; D013535:Suspensions; C005953:monoolein