An investigation of the intradermal route as an effective means of immunization for microparticulate vaccine delivery systems

Among the common routes of parenteral immunization, the skin is the only si te that can function as an immune organ. Skin-associated lymphoid tissue co ntains specialized cells that enhance the immune response. The intercellula r space in the skin interstitium provides a connection to the lymphatic cap illaries and vessels that terminate in peripheral immune organs like the ly mph nodes and spleen. The potential of intradermal immunization with microp articulate vaccine delivery systems was investigated in this study. The mic roparticulates used were muramyl dipeptide (MDP) loaded ovalbumin microsphe res (OVA-MSs) and fluorescent latex microspheres of fixed sizes of 2.3 and 2.1 mu m diameter, respectively. Similar doses of OVA-MSs were injected sub cutaneously (sc) and intradermally lid) in mice. The induced OVA-specific I gG antibody immune response was round to be significantly higher in id immu nized mice as compared to those injected sc. The sc and id administration o f fluorescent latex microspheres in mice demonstrated that the uptake and t ranslocation of microspheres from the: site of injection depends primarily upon the surface area of the microspheres. The enhancement in antibody prod uction upon id administration was explained on the basis of (i) an increase d surface area of microspheres and a lower number of microspheres per injec tion site, and (ii) an increased probability of interaction with the immune cells of the skin. Efficient lymph node targeting observed from the id adm inistered microspheres may be the result of both of these factors. The resu lts of this study demonstrated that the intradermal route is an effective m eans of immunization for microparticulate vaccine delivery systems, requiri ng lower doses and resulting in a higher immune response as compared to the traditionally used sc route. (C) 2000 Elsevier Science Ltd. All rights res erved.