Nasal and parenteral immunizations with diphtheria toxoid using monoglyceride/fatty acid lipid suspensions as adjuvants

A novel suspension system was developed where monoglycerides were formulate d together with fatty acids and subsequently admired with antigens. In the present study, diphtheria toroid was used as a model antigen primarily due to its weak immunological properties as well as to its importance as a futu re human vaccine for mucosal, particularly nasal immunization. The formulat ions were administered parenterally and/or nasally to mice whereafter the i mmune response was determined. In the present study, we have shown that mon o-olein/oleic acid vesicles enhance the immunogenicity of admired diphtheri a toroid in mice to the same level as Alum adsorbed (or Freund's complete a djuvant) 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, shorte r acyl chains also gave rise to more pronounced toxic reactions at the inje ctions 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 immunologic al adjuvant with an exceptionally simple and efficient preparation procedur e without organic solvents and with low cost endogenous lipid based raw mat erials, (C) 1999 Elsevier Science Ltd. All rights reserved.