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 microm diameter, respectively. Similar doses of OVA-MSs were injected subcutaneously (s.c.) and intradermally (i.d.) in mice. The induced OVA-specific IgG antibody immune response was found to be significantly higher in i.d. immunized mice as compared to those injected s.c. The sc and i.d. 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 i.d. 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.
Puri
N
N
College of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Weyand
E H
EH
Abdel-Rahman
S M
SM
Sinko
P J
PJ
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005069:Evaluation Studies as Topic; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007840:Latex; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000098:blood supply / Q000737:chemistry; D051379:Mice; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010316:Particle Size; D012867:Skin / Q000098:blood supply; D014018:Tissue Distribution; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007840:Latex; D014612:Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D010047:Ovalbumin