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阳离子脂质体作为亚单位流感疫苗佐剂的作用：抗原加载方法、胆固醇和免疫调节剂的影响。

Adjuvant effect of cationic liposomes for subunit influenza vaccine: influence of antigen loading method, cholesterol and immune modulators.

机构信息

Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, RA Leiden 2300, The Netherlands.

出版信息

Pharmaceutics. 2013 Jul 25;5(3):392-410. doi: 10.3390/pharmaceutics5030392.

DOI:10.3390/pharmaceutics5030392
PMID:24300513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3836624/
Abstract

Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol) backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation) and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol) and a cationic compound (DC-Chol, DDA, or eDPPC) were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod). The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1) liposome-adsorbed HA is more immunogenic than encapsulated HA; (2) the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3) CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel.

摘要

阳离子脂质体是流感疫苗的潜在佐剂。在之前的一项研究中，我们报告了在一组负载流感血凝素 (HA) 的阳离子脂质体中，DC-Chol:DPPC（1:1 摩尔比）脂质体诱导了最强的免疫反应。然而，尚不清楚胆固醇 (Chol) 主链还是 DC-Chol 的叔胺头基负责这一点。因此，在本工作中，我们研究了 Chol 在阳离子脂质体脂质双层中的影响。此外，我们研究了 HA 加载方法（吸附与包封）和免疫调节剂在 DC-Chol 脂质体中的包封对 HA 免疫原性的影响。由中性脂质（DPPC 或 Chol）和阳离子化合物（DC-Chol、DDA 或 eDPPC）组成的脂质体通过薄膜水化-挤压法制备，有/没有包封的免疫调节剂（CpG 或咪喹莫特）。这些脂质体通常具有相似的粒径分布、ζ 电位和 HA 负载。单核细胞来源的人树突状细胞的体外研究和 C57Bl/6 小鼠的免疫研究表明：(1) 脂质体吸附的 HA 比包封的 HA 更具免疫原性；(2) Chol 掺入阳离子脂质体的双层可增强其佐剂作用；(3) 负载 CpG 的脂质体比普通脂质体或 Alhydrogel 更有效地增强 HA 特异性体液反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/136167a5b2c3/pharmaceutics-05-00392-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/437cdc955f00/pharmaceutics-05-00392-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/3d5725152515/pharmaceutics-05-00392-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/966a9ead51fa/pharmaceutics-05-00392-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/cf1aa5816790/pharmaceutics-05-00392-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/136167a5b2c3/pharmaceutics-05-00392-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/437cdc955f00/pharmaceutics-05-00392-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/3d5725152515/pharmaceutics-05-00392-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/966a9ead51fa/pharmaceutics-05-00392-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/cf1aa5816790/pharmaceutics-05-00392-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3836624/136167a5b2c3/pharmaceutics-05-00392-g005.jpg

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本文引用的文献

[1]
A case-study investigating the physicochemical characteristics that dictate the function of a liposomal adjuvant.

Hum Vaccin Immunother. 2013-4-12

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Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses.

J Control Release. 2012-11-8

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Cationic liposomes as adjuvants for influenza hemagglutinin: more than charge alone.

Eur J Pharm Biopharm. 2012-4-2

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J Control Release. 2012-1-5

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Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: adjuvant- and site-dependent immunogenicity in mice.

Eur J Pharm Sci. 2011-10-8

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