Adjuvant effect of cationic liposomes for subunit influenza vaccine: influence of antigen loading method, cholesterol and immune modulators.
Adjuvant effect of cationic liposomes for subunit influenza vaccine: influence of antigen loading method, cholesterol and immune modulators.
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DOI：
10.3390/pharmaceutics5030392
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发表时间：
2013-07-25
期刊：
影响因子：
5.4
通讯作者：
Jiskoot W
中科院分区：
文献类型：
--
作者：
Barnier-Quer C;Elsharkawy A;Romeijn S;Kros A;Jiskoot W
阳离子脂质体是流感疫苗的潜在佐剂。在先前的研究中，我们报道了在一组负载有流感血凝素（HA）的阳离子脂质体中，DC-Chol：DPPC（1：1摩尔比）脂质体诱导最强的免疫应答。然而，尚不清楚是胆固醇（Chol）骨架还是DC-Chol的叔胺头部基团对此负责。因此，在本工作中，我们研究了Chol在阳离子脂质体的脂双层中的影响。此外，我们研究了HA负载方法（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）组成的脂质体通过具有/不具有包封的免疫调节剂（CpG或咪喹莫特）的膜水合挤出来产生。脂质体通常显示出相当的尺寸分布、zeta电位和HA负载。用单核细胞衍生的人树突状细胞进行的体外研究和在C57 B1/6小鼠中进行的免疫研究表明：（1）脂质体吸附的HA比包封的HA更具免疫原性;（2）在阳离子脂质体的双层中掺入Chol增强了它们的佐剂效应;以及（3）CpG负载的脂质体比普通脂质体或铝胶更有效地增强HA特异性体液应答。
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.