Administration routes affect the quality of immune responses: a cross-sectional evaluation of particulate antigen-delivery systems

Deepa Mohanan, Bram Slütter, Malou Henriksen-Lacey, Wim Jiskoot, Joke A Bouwstra, Yvonne Perrie, Thomas M. Kündig, Bruno Gander, Pål Johansen

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Particulate delivery systems such as liposomes and polymeric nano- and microparticles are attracting great interest for developing new vaccines. Materials and formulation properties essential for this purpose have been extensively studied, but relatively little is known about the influence of the administration route of such delivery systems on the type and strength of immune response elicited. Thus, the present study aimed at elucidating the influence on the immune response when of immunising mice by different routes, such as the subcutaneous, intradermal, intramuscular, and intralymphatic routes with ovalbumin-loaded liposomes, N-trimethyl chitosan (TMC) nanoparticles, and poly(lactide-co-glycolide) (PLGA) microparticles, all with and without specifically selected immune-response modifiers. The results showed that the route of administration caused only minor differences in inducing an antibody response of the IgG1 subclass, and any such differences were abolished upon booster immunisation with the various adjuvanted and non-adjuvanted delivery systems. In contrast, the administration route strongly affected both the kinetics and magnitude of the IgG2a response. A single intralymphatic administration of all evaluated delivery systems induced a robust IgG2a response, whereas subcutaneous administration failed to elicit a substantial IgG2a response even after boosting, except with the adjuvanted nanoparticles. The intradermal and intramuscular routes generated intermediate IgG2a titers. The benefit of the intralymphatic administration route for eliciting a Th1-type response was confirmed in terms of IFN-gamma production of isolated and re-stimulated splenocytes from animals previously immunised with adjuvanted and non-adjuvanted liposomes as well as with adjuvanted microparticles. Altogether the results show that the IgG2a associated with Th1-type immune responses are sensitive to the route of administration, whereas IgG1 response associated with Th2-type immune responses were relatively insensitive to the administration route of the particulate delivery systems. The route of administration should therefore be considered when planning and interpreting pre-clinical research or development on vaccine delivery systems.
Original languageEnglish
Pages (from-to)342-349
Number of pages8
JournalJournal of Controlled Release
Issue number3
Early online date18 Aug 2010
Publication statusPublished - 1 Nov 2010


  • immunologic adjuvants
  • animals
  • cultured cells
  • pharmaceutical chemistry
  • chitosan
  • drug administration routes
  • drug carriers
  • drug delivery systems
  • female
  • immunoglobulin G
  • interferon-gamma
  • kinetics
  • lactic acid
  • liposomes
  • mice
  • inbred BALB C mice
  • nanoparticles
  • ovalbumin
  • particle Size
  • polyglycolic acid
  • solubility
  • spleen
  • Th1 cells
  • Th2 cells
  • time factors
  • vaccines


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