Adjuvant properties of non-phospholipid liposomes (Novasomes(R)) in experimental animals for human vaccine antigens
Adjuvant properties of non-phospholipid liposomes (Novasomes(R)) in experimental animals for human vaccine antigens
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DOI：
10.1016/0264-410x(95)00182-z
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发表时间：
1996-02-01
期刊：
影响因子：
5.5
通讯作者：
Siber, GR
中科院分区：
文献类型：
--
作者：
Gupta, RK;Varanelli, CL;Siber, GR
由二氧乙烯十六烷基醚、胆固醇和油酸组成的非磷脂脂质体作为人疫苗抗原，破伤风类毒素（TT）和白喉类毒素（DT）的佐剂，在小鼠和家兔中进行了评价。包裹在脂质体中或与脂质体混合的抗原引起的抗毒素水平与用弗氏佐剂给予或吸附在磷酸铝上的抗原引起的抗毒素水平相似。所有脂质体抗原制剂，与弗氏佐剂一起给药或吸附在磷酸铝上的抗原，在单次注射后小鼠和三次注射后兔体内的IgG抗体和抗毒素水平均显著高于可溶性抗原。与与脂质体混合的TT相比，单次注射后，包裹在脂质体中的TT在小鼠体内引起持续的抗TT IgG抗体水平。TT与含有单磷酰脂质A/角鲨烯或单独含有角鲨烯的脂质体混合或包封在脂质体内，以及磷酸铝吸附的TT在小鼠中引起的原发性反应比与普通脂质体混合或包封在脂质体内的TT更大。脂质体TT制剂在小鼠中产生的遗忘反应略高于磷酸铝吸附TT。抗tt抗体亚类分析显示，大部分抗体属于IGG1亚类。脂质体TT制剂，特别是包封单磷脂酰脂A/角鲨烯或单角鲨烯的TT制剂，始终比磷酸铝吸附或可溶性TT诱导更高水平的抗TT IgG2a和IgG2b。这些制剂均未引起IgG3或IgM抗体。非磷脂脂质体似乎与目前用于人类疫苗的佐剂（磷酸铝）或实验免疫学的基准佐剂（弗氏佐剂）一样是有效的佐剂，并且可能能够调节对Thl型的免疫反应。
Non-phospholipid liposomes composed of dioxyethylene cetyl ether, cholesterol and oleic acid were evaluated as adjuvants with human vaccine antigens, tetanus toxoid (TT) and diphtheria toxoid (DT), in mice and rabbits. Antigens encapsulated in or mixed with liposomes elicited antitoxin levels similar to those elicited by antigens given with Freund's adjuvant or adsorbed onto aluminum phosphate. All liposomal antigen preparations, antigen given with Freund's adjuvant or adsorbed onto aluminum phosphate, elicited significantly higher IgG antibodies and antitoxin levels than soluble antigens in mice after a single injection and in rabbits after each of three injections. TT encapsulated in liposomes elicited sustained anti-TT IgG antibody levels in mice after a single injections as compared to TT mixed with liposomes. TT mixed with or encapsulated within liposomes containing monophosphoryl lipid A/squalene or squalene alone, as well as aluminum phosphate adsorbed TT elicited greater primary responses in mice than TT mixed with or encapsulated within plain liposomes. Liposomal TT preparations produced a slightly higher anamnestic response in mice than aluminum phosphate adsorbed TT. Subclass analysis of anti-TT antibodies showed that the majority of the antibodies belong to IGG1 subclass. Liposomal TT preparations, particularly those with encapsulated monophosphoryl lipid A/squalene or squalene alone, consistently elicited higher levels of anti-TT IgG2a and IgG2b than aluminum phosphate adsorbed or soluble TT. None of the preparations elicited IgG3 or IgM antibodies. It appears that non-phospholipid liposomes are as potent adjuvants as the currently employed adjuvant for human vaccines (aluminum phosphate) or a benchmark adjuvant for experimental immunology (Freund's adjuvant), and may be able to modulate the immune response towards the Thl type.