A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog
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A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog. / Christensen, Dennis; Henriksen-Lacey, Malou; Kamath, Arun T; Lindenstrøm, Thomas; Korsholm, Karen S; Christensen, Jan Pravsgaard; Rochat, Anne-Francoise; Lambert, Paul-Henri; Andersen, Peter; Siegrist, Claire-Anne; Perrie, Yvonne; Agger, Else Marie.
In: Journal of controlled release : official journal of the Controlled Release Society, Vol. 160, No. 3, 06.2012, p. 468-476.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog
AU - Christensen, Dennis
AU - Henriksen-Lacey, Malou
AU - Kamath, Arun T
AU - Lindenstrøm, Thomas
AU - Korsholm, Karen S
AU - Christensen, Jan Pravsgaard
AU - Rochat, Anne-Francoise
AU - Lambert, Paul-Henri
AU - Andersen, Peter
AU - Siegrist, Claire-Anne
AU - Perrie, Yvonne
AU - Agger, Else Marie
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.
AB - Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response.
U2 - 10.1016/j.jconrel.2012.03.016
DO - 10.1016/j.jconrel.2012.03.016
M3 - Journal article
C2 - 22709414
VL - 160
SP - 468
EP - 476
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -
ID: 38493629