Gupta R K, Varanelli C L, Griffin P, Wallach D F, Siber G R
Massachusetts Public Health Biologic Laboratories, State Laboratory Institute, Boston 02130, USA.
Vaccine. 1996 Feb;14(3):219-25. doi: 10.1016/0264-410x(95)00182-z.
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 injection 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 Th1 type.
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，作为佐剂与人类疫苗抗原破伤风类毒素（TT）和白喉类毒素（DT）一起在小鼠和兔子身上进行了评估。包封在脂质体中或与脂质体混合的抗原所引发的抗毒素水平，与用弗氏佐剂给予或吸附在磷酸铝上的抗原所引发的抗毒素水平相似。所有脂质体抗原制剂、用弗氏佐剂给予的抗原或吸附在磷酸铝上的抗原，在小鼠单次注射后以及兔子三次注射中的每次注射后，所引发的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，包封在脂质体中的TT在小鼠单次注射后能引发持续的抗TT IgG抗体水平。与单磷酰脂质A/角鲨烯或仅含角鲨烯的脂质体混合或包封的TT，以及吸附在磷酸铝上的TT，在小鼠中引发的初次反应比与普通脂质体混合或包封的TT更大。脂质体TT制剂在小鼠中产生的回忆反应略高于吸附在磷酸铝上的TT。抗TT抗体的亚类分析表明，大多数抗体属于IgG1亚类。脂质体TT制剂，特别是那些仅包封单磷酰脂质A/角鲨烯或角鲨烯的制剂，始终比吸附在磷酸铝上的或可溶性的TT引发更高水平的抗TT IgG2a和IgG2b。没有一种制剂引发IgG3或IgM抗体。看来非磷脂脂质体作为佐剂的效力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）相当，并且可能能够调节免疫反应向Th1型发展。
