LIPOSOMAL MALARIA VACCINE IN HUMANS - A SAFE AND POTENT ADJUVANT STRATEGY
LIPOSOMAL MALARIA VACCINE IN HUMANS - A SAFE AND POTENT ADJUVANT STRATEGY
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DOI：
10.1073/pnas.89.1.358
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发表时间：
1992-01-01
影响因子：
11.1
通讯作者：
ALVING, CR
中科院分区：
文献类型：
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作者：
FRIES, LF;GORDON, DM;ALVING, CR
这项研究描述了注入人类受试者的基于脂质体的疫苗的安全性和免疫原性。用脂质体封装的重组蛋白（R32NS1（81））对三十名健康的成年男性志愿者进行免疫，其中含有来自法氏疟原虫的外孢子菌蛋白重复区域的表位。此前，这种抗原在人类中被Al（OH）3吸附时，这种抗原在人类中的免疫原性很差。在本研究中，将R32NS1（81）封装在含有单磷酸脂质A的脂质体中，随后吸附到Al（OH）3。使用了含有抗原和单磷酸脂质A的剂量的增加，但脂质体始终被吸附至相同剂量的Al（OH）3。 R32特异性的血清IgG抗体对脂质体封装的R32NS1（81）的抗体反应远高于先前在R32NS1（R32NS1（81））中所获得的水平（81）。三剂剂量后的几何平均特异性IgG水平范围为14至33 mu-g/ml。接受两种最高剂量的志愿者的血清抑制了恶性疟原虫孢子岩侵袭培养的肝癌细胞的侵袭，平均抑制了92％的培养的肝癌细胞，这一结果再次优于先前报道的疫苗。在高剂量的疫苗制剂中，注意到中度但可接受的瞬时局部反应性，但是尽管脂质体单磷酸脂质A剂量为2200 mU-g，但几乎没有或没有全身毒性。我们得出的结论是，在单磷酸脂质A的脂质体中，免疫原性的割孢子蛋白重复肽重复肽的封装是人类成功的辅助策略，用于诱导高水平的特定抗体产生。
This study describes the safety and immunogenicity of a liposome-based vaccine injected into human subjects. Thirty healthy adult male volunteers were immunized with a liposome-encapsulated recombinant protein (R32NS1(81)) containing epitopes from the repeat region of the circumsporozoite protein of Plasmodium falciparum. This antigen had previously been found to be poorly immunogenic in humans when it was adsorbed with Al(OH)3. In the present study, R32NS1(81) was encapsulated in liposomes containing monophosphoryl lipid A that were subsequently adsorbed to Al(OH)3. Increasing doses of liposomes containing antigen and monophosphoryl lipid A were used, but the liposomes were always adsorbed to the same dose of Al(OH)3. R32-specific serum IgG antibody responses to liposome-encapsulated R32NS1(81) were much higher than levels attained previously in humans with R32NS1(81) adsorbed to Al(OH)3. Geometric mean specific IgG levels after three doses ranged from 14 to 33-mu-g/ml. Sera from volunteers receiving the two highest doses inhibited P. falciparum sporozoite invasion of cultured hepatoma cells by an average of 92%, a result that was again superior to previously reported vaccines. Moderate but acceptable transient local reactogenicity was noted at high doses of the vaccine formulation, but little or no systemic toxicity was seen despite liposomal monophosphoryl lipid A doses up to 2200-mu-g. We conclude that encapsulation of poorly immunogenic circumsporozoite protein repeat peptides in monophosphoryl lipid A-containing liposomes is a successful adjuvant strategy in humans for inducing high levels of specific antibody production.