Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine.
Immunogenicity and in vitro protective efficacy of a recombinant multistage Plasmodium falciparum candidate vaccine.
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DOI：
10.1073/pnas.96.4.1615
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发表时间：
1999-02
影响因子：
11.1
通讯作者：
Y. Shi;Seyed E. Hasnain;J. Sacci;Brian P. Holloway;Hisashi Fujioka;Nirbhay Kumar;Robert M. Wohlhueter;S. L. Hoffman;William E. Collins;A. Lal
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文献类型：
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作者：
Y. Shi;Seyed E. Hasnain;J. Sacci;Brian P. Holloway;Hisashi Fujioka;Nirbhay Kumar;Robert M. Wohlhueter;S. L. Hoffman;William E. Collins;A. Lal
与单阶段抗原疫苗相比，多阶段和多价恶性疟原虫疫苗通过诱导“多层”免疫而更有效。我们已经构建了一个合成基因，编码12个B细胞，6个T细胞增殖，和3个细胞毒性T淋巴细胞表位，来自9个阶段特异性恶性疟原虫抗原，对应于子孢子，肝脏，红细胞无性，和有性阶段。该基因在杆状病毒系统中表达，并纯化了41-kDa的抗原，称为CDC/NIIMALVAC-1。在存在不同佐剂的情况下，用纯化的蛋白质在兔中进行免疫接种产生了识别疫苗抗原、疫苗中所含的线性肽和恶性疟原虫的所有阶段的抗体应答。体外保护试验表明，疫苗引起的抗体强烈抑制子孢子侵入肝癌细胞和血液阶段的寄生虫在单核细胞的存在下的生长。这些观察结果表明，多组分、多阶段疟疾疫苗可以诱导免疫应答，在多个阶段抑制寄生虫的发育。在多组分恶性疟原虫疫苗的开发中使用的原理和方法将有助于多物种人疟疾疫苗和针对其他传染病的疫苗的开发。
Compared with a single-stage antigen-based vaccine, a multistage and multivalent Plasmodium falciparum vaccine would be more efficacious by inducing "multiple layers" of immunity. We have constructed a synthetic gene that encodes for 12 B cell, 6 T cell proliferative, and 3 cytotoxic T lymphocyte epitopes derived from 9 stage-specific P. falciparum antigens corresponding to the sporozoite, liver, erythrocytic asexual, and sexual stages. The gene was expressed in the baculovirus system, and a 41-kDa antigen, termed CDC/NIIMALVAC-1, was purified. Immunization in rabbits with the purified protein in the presence of different adjuvants generated antibody responses that recognized vaccine antigen, linear peptides contained in the vaccine, and all stages of P. falciparum. In vitro assays of protection revealed that the vaccine-elicited antibodies strongly inhibited sporozoite invasion of hepatoma cells and growth of blood-stage parasites in the presence of monocytes. These observations demonstrate that a multicomponent, multistage malaria vaccine can induce immune responses that inhibit parasite development at multiple stages. The rationale and approach used in the development of a multicomponent P. falciparum vaccine will be useful in the development of a multispecies human malaria vaccine and vaccines against other infectious diseases.