The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab-restricted: possible implications for malaria vaccines.
The antibody response in mice to carrier-free synthetic polymers of Plasmodium falciparum circumsporozoite repetitive epitope is I-Ab-restricted: possible implications for malaria vaccines.
复制标题
小鼠对恶性疟原虫环子孢子重复表位的无载体合成聚合物的抗体反应是 I-Ab 限制的：这可能对疟疾疫苗产生影响。
作者：
G. Del Giudice;J. Cooper;J. Merino;A. Verdini;A. Pessi;A. R. Togna;H. Engers;G. Corradin;P. Lambert
在不使用任何载体蛋白的情况下，研究了由恶性疟原虫环孢子子蛋白（NANP）40的平均40个（Asn-Ala-Asn-Pro）重复序列组成的新型合成肽的免疫原性。首先，C57BL/6小鼠免疫后可获得高滴度的抗（NANP）40抗体。这些抗体还与感染恶性疟原虫孢子虫的蚊子提取物发生反应。C57BL/6 nu/nu小鼠不产生（NANP）40抗体。其次，用（NANP）40免疫14株9种不同H-2单倍型小鼠时，发现只有H-2b小鼠产生抗（NANP）40抗体，而所有非H-2b小鼠均无反应。通过重组小鼠和突变小鼠，证实了这种反应与i - a连锁。I-Ab [B10。A(5R)]小鼠和H-2b近交系小鼠均产生抗（NANP）40抗体。B6CH-2bm12 i - ab突变小鼠仅表现出非常低的反应。第三，将NANP - 40与载体蛋白偶联免疫，可诱导无应答小鼠产生抗体应答。鉴于在小鼠体内对孢子子合成多肽的反应中存在这种特殊的H-2b限制，在接受孢子子疟疾疫苗的人体内触发肽特异性T细胞反应可能很难实现。
The immunogenicity of a novel synthetic peptide consisting of an average of 40 (Asn-Ala-Asn-Pro) repeats of the circumsporozoite protein of Plasmodium falciparum, (NANP)40, was studied in mice without using any carrier proteins. First, high titers of anti-(NANP)40 antibodies could be obtained after immunization of C57BL/6 mice. These antibodies also reacted with an extract of mosquitoes infected with P. falciparum sporozoites. C57BL/6 nu/nu mice did not produce antibodies against (NANP)40. Secondly, when 14 strains of mice with nine different H-2 haplotypes were immunized with (NANP)40 without carrier, only H-2b mice were found to produce anti-(NANP)40 antibodies, whereas all non-H-2b mice were consistently unresponsive. This response was demonstrated to be I-A-linked by using recombinant and mutant mice. I-Ab [B10.A(5R)] mice produced anti-(NANP)40 antibodies as well as H-2b inbred mice. B6CH-2bm12 I-Ab-mutant mice showed only a very low response. Third, the antibody response against (NANP)40 could be induced in nonresponder mice by immunization with the peptide coupled to a carrier protein. In view of the existence of such an exceptional H-2b restriction in the response to sporozoite synthetic peptides in mice, the triggering of peptide-specific T cell responses in humans receiving sporozoite malaria vaccines might be difficult to achieve.