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重组生产的恶性疟原虫环子孢子蛋白-乙型肝炎表面抗原亚单位疫苗的安全性、免疫原性和有效性。

Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine.

作者信息

Gordon D M, McGovern T W, Krzych U, Cohen J C, Schneider I, LaChance R, Heppner D G, Yuan G, Hollingdale M, Slaoui M

机构信息

Department of Immunology, Walter Reed Army Institute of Research, Washington, DC, USA.

出版信息

J Infect Dis. 1995 Jun;171(6):1576-85. doi: 10.1093/infdis/171.6.1576.

DOI:10.1093/infdis/171.6.1576
PMID:7769295
Abstract

Twenty malaria-naive volunteers received a recombinant Plasmodium falciparum malaria vaccine (RTS,S) containing 19 NANP repeats and the carboxy terminus (amino acids 210-398) of the circumsporozoite (CS) antigen coexpressed in yeast with hepatitis B surface antigen. Ten received vaccine adjuvanted with alum, and 10 received vaccine adjuvanted with alum plus 3-deacylated monophosphoryl lipid A (MPL). Both formulations were well tolerated and immunogenic. MPL enhanced CS antibody levels (measured by ELISA, immunofluorescence, and inhibition of sporozoite invasion assays). After sporozoite challenge, 6 of 6 in the alum group and 6 of 8 in the alum-MPL group developed patent malaria. Protected subjects had higher levels of CS antibody titers on day of challenge than did nonprotected subjects. After immunization, 1 protected subject had increased cytotoxic T lymphocyte activity against CS and recall of memory T cell responses to RTS,S and selected CS.

摘要

20名未曾感染过疟疾的志愿者接种了一种重组恶性疟原虫疟疾疫苗(RTS,S),该疫苗含有19个NANP重复序列以及环子孢子蛋白(CS)抗原的羧基末端(氨基酸210 - 398),它与乙肝表面抗原在酵母中共表达。10名志愿者接种了含明矾佐剂的疫苗,另外10名接种了含明矾加3 - 脱酰基单磷酰脂质A(MPL)佐剂的疫苗。两种配方耐受性良好且具有免疫原性。MPL提高了CS抗体水平(通过酶联免疫吸附测定、免疫荧光和抑制子孢子入侵试验进行测量)。在子孢子攻击后,明矾组6名受试者中的6名以及明矾 - MPL组8名受试者中的6名出现了明显的疟疾症状。受到保护的受试者在攻击当天的CS抗体滴度水平高于未受保护的受试者。免疫后,1名受保护的受试者对CS的细胞毒性T淋巴细胞活性增强,并且对RTS,S和选定的CS的记忆T细胞反应出现回忆。

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