The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses: the immunological consequences of the biodistribution profile

Signe Tandrup Schmidt, Swapnil Khadke, Karen Smith Korsholm, Yvonne Perrie, Thomas Rades, Peter Andersen, Camilla Foged, Dennis Christensen*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

A prerequisite for vaccine-mediated induction of CD8+ T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8+ T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8+ T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8+ T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i.p. immunization, is required for the subsequent activation of cross-presenting lymphoid organ-resident CD8α+ DCs. In contrast, s.c. or i.m. immunization usually results in the formation of a depot at the site of injection (SOI), which hinders the self-drainage and targeting of the vaccine to cross-presenting CD8α+ DCs. We investigated this hypothesis by correlating the biodistribution pattern and the adjuvanticity of the strong CD8+ T-cell inducing liposomal cationic adjuvant formulation 09 (CAF09), which is composed of dimethyldioctadecylammonium bromide/monomycoloyl glycerol liposomes with polyinosinic:polycytidylic acid electrostatically adsorbed to the surface. Biodistribution studies with radiolabeled CAF09 and a surface-adsorbed model antigen [ovalbumin (OVA)] showed that a significantly larger fraction of the vaccine dose localized in the draining lymph nodes (dLNs) and the spleen 6 h after i.p. immunization, as compared to after i.m. immunization. Studies with fluorescently labelled OVA + CAF09 demonstrated a preferential association of OVA + CAF09 to DCs/monocytes, as compared to macrophages and B cells, following i.p. immunization. Administration of OVA + CAF09 via the i.p. route did also result in DC activation, whereas no DC activation could be measured within the same period with unadjuvanted OVA and OVA + CAF09 administered via the s.c. or i.m. routes. In the dLNs, the highest level of activated, cross-presenting CD8α+ DCs was detected at 24 h post immunization, whereas an influx of activated, migrating and cross-presenting CD103+ DCs to the dLNs could be measured after 48 h. This suggests that the CD8α+ DCs are activated by self-draining OVA + CAF09 in the lymphoid organs, whereas the CD103+ DCs are stimulated by the OVA + CAF09 at the SOI. These results support the hypothesis that the self-drainage of OVA + CAF09 to the draining LNs is required for the activation of CD8α+ DCs, while the migratory CD103+ DCs may play a role in sustaining the subsequent induction of strong CD8+ T-cell responses.
Original languageEnglish
Pages (from-to)107–117
Number of pages11
JournalJournal of Controlled Release
Volume239
Early online date26 Aug 2016
DOIs
Publication statusPublished - 10 Oct 2016

Fingerprint

CD8 Antigens
Ovalbumin
Vaccines
T-Lymphocytes
Immunization
Dendritic Cells
Drainage
Lymph Nodes
Antigens
Poly I-C
Injections
Liposomes
Epitopes
Monocytes
B-Lymphocytes
Spleen
Macrophages

Bibliographical note

© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.jconrel.2016.08.034

Keywords

  • liposome
  • subunit vaccine
  • biodistribution
  • cross-presentation
  • adjuvant
  • nanomedicine

Cite this

Tandrup Schmidt, Signe ; Khadke, Swapnil ; Smith Korsholm, Karen ; Perrie, Yvonne ; Rades, Thomas ; Andersen, Peter ; Foged, Camilla ; Christensen, Dennis. / The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses : the immunological consequences of the biodistribution profile. In: Journal of Controlled Release. 2016 ; Vol. 239. pp. 107–117.
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The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses : the immunological consequences of the biodistribution profile. / Tandrup Schmidt, Signe; Khadke, Swapnil; Smith Korsholm, Karen; Perrie, Yvonne; Rades, Thomas; Andersen, Peter; Foged, Camilla; Christensen, Dennis.

In: Journal of Controlled Release, Vol. 239, 10.10.2016, p. 107–117.

Research output: Contribution to journalArticle

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AU - Khadke, Swapnil

AU - Smith Korsholm, Karen

AU - Perrie, Yvonne

AU - Rades, Thomas

AU - Andersen, Peter

AU - Foged, Camilla

AU - Christensen, Dennis

N1 - © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.jconrel.2016.08.034

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