SAFETY AND IMMUNOGENICITY IN VOLUNTEERS OF A RECOMBINANT PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN MALARIA VACCINE PRODUCED IN LEPIDOPTERAN CELLS
SAFETY AND IMMUNOGENICITY IN VOLUNTEERS OF A RECOMBINANT PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN MALARIA VACCINE PRODUCED IN LEPIDOPTERAN CELLS
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DOI：
10.1016/0264-410x(92)90047-n
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发表时间：
1992-01-01
期刊：
影响因子：
5.5
通讯作者：
EDELMAN, R
中科院分区：
文献类型：
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作者：
HERRINGTON, DA;LOSONSKY, GA;EDELMAN, R
利用含有恶性疟原虫环孢子子（CS）全基因的杆状病毒表达载体，在昆虫细胞中制备了重组恶性疟原虫环孢子子抗原（rPfCSA）。这种接近全长的CS抗原被吸附在磷酸铝上，用作疟疾疫苗。在一项安全性和免疫原性的研究中，20名志愿者被分成4组，每组5人，分别肌肉注射10、100、500或1000 μ g的疫苗。初次接种后，在2个月和6个月进行两次加强免疫。三名志愿者在第二次或第三次接种疫苗后出现明显的局部反应，表现为注射部位的压痛、红肿。所有症状在72小时内自行消退。使用rPfCSA作为抗原，20名志愿者中有6名的刺激后血清经Western blot检测显示血清转化。然而，对完整的孢子子进行间接免疫荧光或利用rPfCSA或肽段对重复区进行ELISA检测，无法检测到特异性的抗cs蛋白抗体。此外，通过ELISA和/或Western blot检测，20名志愿者中有18人产生了杆状病毒蛋白抗体。抗原驱动复制研究使用来自疫苗的外周血单个核细胞未能检测到CS蛋白特异性的增殖反应。这种重组CS蛋白疫苗在人体中具有最低限度的免疫原性。
A recombinant Plasmodium falciparum circumsporozoite (CS) antigen (rPfCSA) was produced in insect cells using a baculovirus expression vector containing the entire CS gene. This near full-length CS antigen was adsorbed onto aluminium phosphate for use as a malaria vaccine. In a study of safety and immunogenicity, 20 volunteers were divided into four groups of five each and inoculated intramuscularly with 10, 100, 500 or 1000-mu-g of vaccine. Primary vaccinations were followed by two booster immunizations at 2 and 6 months. Three volunteers developed prominent local reactions manifested as tenderness, redness and swelling at the injection site following the second or third vaccination. All symptoms resolved spontaneously within 72 h. Postimmunization sera from six of 20 volunteers showed seroconversions as measured by Western blot, using rPfCSA as antigen. However, specific anti-CS protein antibody could not be detected by indirect immunoflourescence against intact sporozoites or by ELISA using rPfCSA or peptide to the repeat region. In addition, 18 of 20 volunteers developed antibody to baculovirus proteins as determined by ELISA and/or Western blot. Antigen-driven replication studies using peripheral blood mononuclear cells from vaccinees failed to detect proliferative responses specific to CS protein. This recombinant CS protein vaccine, as formulated, was minimally immunogenic in humans.