Abstract
Language | English |
---|---|
Pages | 107-117 |
Number of pages | 11 |
Journal | Journal of Controlled Release |
Volume | 239 |
Early online date | 26 Aug 2016 |
DOIs | |
Publication status | Published - 10 Oct 2016 |
Fingerprint
Keywords
- liposome
- subunit vaccine
- biodistribribution
- cross-presentation
- adjuvant
- nanomedicine
Cite this
}
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. / Schmidt, Signe Tandrup; Khadke, Swapnil; Korsholm, Karen Smith; 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 journal › Article
TY - JOUR
T1 - The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses
T2 - Journal of Controlled Release
AU - Schmidt, Signe Tandrup
AU - Khadke, Swapnil
AU - Korsholm, Karen Smith
AU - Perrie, Yvonne
AU - Rades, Thomas
AU - Andersen, Peter
AU - Foged, Camilla
AU - Christensen, Dennis
N1 - Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2016/10/10
Y1 - 2016/10/10
N2 - 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.
AB - 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.
KW - liposome
KW - subunit vaccine
KW - biodistribribution
KW - cross-presentation
KW - adjuvant
KW - nanomedicine
UR - http://www.sciencedirect.com/science/journal/01683659
U2 - 10.1016/j.jconrel.2016.08.034
DO - 10.1016/j.jconrel.2016.08.034
M3 - Article
VL - 239
SP - 107
EP - 117
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -