Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response

Malou Henriksen-Lacey, Dennis Christensen, Vincent W. Bramwell, Thomas Lindenstrøm, Else Marie Agger, Peter Andersen, Yvonne Perrie

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50%) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response.

LanguageEnglish
Pages102-108
Number of pages7
JournalJournal of Controlled Release
Volume145
Issue number2
DOIs
Publication statusPublished - 14 Jul 2010

Fingerprint

Liposomes
Adsorption
Vaccines
Antigens
Injections
T-Cell Antigen Receptor Specificity
Viral Tumor Antigens
Interleukin-5
Antigen Presentation
Lymphoid Tissue
Surface Antigens
Immune System
Cytokines
T-Lymphocytes

Keywords

  • cationic liposomes
  • protein antigen
  • vaccine adjuvant
  • pharmacokinetics
  • immunostimulatory

Cite this

Henriksen-Lacey, Malou ; Christensen, Dennis ; Bramwell, Vincent W. ; Lindenstrøm, Thomas ; Agger, Else Marie ; Andersen, Peter ; Perrie, Yvonne. / Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response. In: Journal of Controlled Release. 2010 ; Vol. 145, No. 2. pp. 102-108.
@article{f21c580225374ef2af00e63dc72eea24,
title = "Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response",
abstract = "With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50{\%}) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response.",
keywords = "cationic liposomes, protein antigen, vaccine adjuvant, pharmacokinetics, immunostimulatory",
author = "Malou Henriksen-Lacey and Dennis Christensen and Bramwell, {Vincent W.} and Thomas Lindenstr{\o}m and Agger, {Else Marie} and Peter Andersen and Yvonne Perrie",
note = "Copyright (c) 2010 Elsevier B.V. All rights reserved.",
year = "2010",
month = "7",
day = "14",
doi = "10.1016/j.jconrel.2010.03.027",
language = "English",
volume = "145",
pages = "102--108",
journal = "Journal of Controlled Release",
issn = "0168-3659",
number = "2",

}

Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response. / Henriksen-Lacey, Malou; Christensen, Dennis; Bramwell, Vincent W.; Lindenstrøm, Thomas; Agger, Else Marie; Andersen, Peter; Perrie, Yvonne.

In: Journal of Controlled Release, Vol. 145, No. 2, 14.07.2010, p. 102-108.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a CMI response

AU - Henriksen-Lacey, Malou

AU - Christensen, Dennis

AU - Bramwell, Vincent W.

AU - Lindenstrøm, Thomas

AU - Agger, Else Marie

AU - Andersen, Peter

AU - Perrie, Yvonne

N1 - Copyright (c) 2010 Elsevier B.V. All rights reserved.

PY - 2010/7/14

Y1 - 2010/7/14

N2 - With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50%) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response.

AB - With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50%) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response.

KW - cationic liposomes

KW - protein antigen

KW - vaccine adjuvant

KW - pharmacokinetics

KW - immunostimulatory

U2 - 10.1016/j.jconrel.2010.03.027

DO - 10.1016/j.jconrel.2010.03.027

M3 - Article

VL - 145

SP - 102

EP - 108

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2

ER -