Hoffman S L, Wistar R, Ballou W R, Hollingdale M R, Wirtz R A, Schneider I, Marwoto H A, Hockmeyer W T
N Engl J Med. 1986 Sep 4;315(10):601-6. doi: 10.1056/NEJM198609043151001.
A candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.
一种候选的恶性疟原虫子孢子疫苗R32tet32已被研制出来，它包含32个源自恶性疟原虫环子孢子蛋白的四肽重复序列。该疫苗的研发基于这样一种假设，即针对该蛋白重复区域的抗体将能预防子孢子感染。两种体外检测方法，即环子孢子沉淀反应和抑制子孢子侵入肝癌细胞的检测结果，被认为可表明保护性免疫。因此，我们检测了来自印度尼西亚一个疟疾高度流行地区人群的血清样本，以检测其针对R32tet32的抗体，以及产生环子孢子沉淀和抑制子孢子侵入肝癌细胞的能力。针对R32tet32的抗体流行率和平均滴度随受试者年龄增加而上升，而该社区中恶性疟原虫感染率则下降。只有IgG或IgM R32tet32抗体滴度大于或等于1/800的血清样本才具有沉淀活性和超过75%的侵入抑制活性。当通过亲和层析对血清样本进行分离时，只有含有纯化的人抗R32tet32抗体的组分才具有这种活性。这些数据支持了以下假设：在疟疾流行地区，针对环子孢子蛋白的抗体对于随着年龄增长降低疟疾流行率很重要；并且疫苗引发的针对环子孢子重复区域的抗体将能预防恶性疟原虫子孢子感染。
