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 site that can function as an immune organ. Skin-associated lymphoid tissue contains specialized cells that enhance the immune response. The intercellular space in the skin interstitium provides a connection to the lymphatic capillaries and vessels that terminate in peripheral immune organs like the lymph nodes and spleen. The potential of intradermal immunization with microparticulate vaccine delivery systems was investigated in this study. The microparticulates used were muramyl dipeptide (MDP) loaded ovalbumin microspheres (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 subcutaneously (sc) and intradermally lid) in mice. The induced OVA-specific IgG antibody immune response was round to be significantly higher in id immunized mice as compared to those injected sc. The sc and id administration of fluorescent latex microspheres in mice demonstrated that the uptake and translocation of microspheres from the: site of injection depends primarily upon the surface area of the microspheres. The enhancement in antibody production upon id administration was explained on the basis of (i) an increased surface area of microspheres and a lower number of microspheres per injection site, and (ii) an increased probability of interaction with the immune cells of the skin. Efficient lymph node targeting observed from the id administered microspheres may be the result of both of these factors. The results of this study demonstrated that the intradermal route is an effective means of immunization for microparticulate vaccine delivery systems, requiring lower doses and resulting in a higher immune response as compared to the traditionally used sc route. (C) 2000 Elsevier Science Ltd. All rights reserved.