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接种疟疾疫苗SPf66的冈比亚儿童体内恶性疟原虫基因型平均数量的减少

Reduction in the mean number of Plasmodium falciparum genotypes in Gambian children immunized with the malaria vaccine SPf66.

作者信息

Haywood M, Conway D J, Weiss H, Metzger W, D'Alessandro U, Snounou G, Targett G, Greenwood B

机构信息

Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.

出版信息

Trans R Soc Trop Med Hyg. 1999 Feb;93 Suppl 1:65-8. doi: 10.1016/s0035-9203(99)90330-9.

DOI:10.1016/s0035-9203(99)90330-9
PMID:10450429
Abstract

SPf66, a synthetic peptide Plasmodium falciparum vaccine, did not protect young Gambian children against clinical attacks of malaria. Nevertheless, Gambian children who had been vaccinated with SPf66 and who were parasitaemic at the end of the first malaria transmission season after vaccination had significantly fewer detectable P. falciparum genotypes than control children, as determined by polymerase chain reaction analysis of 3 polymorphic loci--the msp1 block 2 repeat region, the msp2 repeat region, and the R11 region of the glutamate-rich protein gene (glurp). Geometric mean numbers of genotypes were 1.66 vs. 1.87, 1.95 vs. 2.43, and 1.21 vs. 1.50 for msp1, msp2 and glurp, respectively (P = 0.31, P = 0.04 and P < 0.01). Differences between groups became a little more marked for msp1 and msp2 when children with symptomatic malaria were excluded. No significant difference was found between parasites obtained from SPf66-vaccinated or control children in the prevalences of amino acid alleles at positions 44 and 47 in the 11 amino acid sequence of the merozoite surface protein 1 molecule, which is present in SPf66. The reduction in the number of genotypes observed could not be explained by a difference in parasite densities between SPf66-vaccinated and control children, as geometric mean parasite densities were almost identical in the 2 groups. These observations suggest that SPf66 vaccine may have induced an immune response which reduced the incidence of new infections in immunized children or accelerated the rate of clearance of parasites of individual genotypes. However, no reduction in the prevalence or density of parasitaemia was recorded in SPf66-vaccinated children, suggesting the existence of some kind of density-dependent mechanism for controlling low levels of malaria parasitaemia.

摘要

SPf66是一种合成肽恶性疟原虫疫苗,未能保护冈比亚幼儿免受疟疾的临床发作。然而,接种SPf66疫苗且在接种后第一个疟疾传播季节结束时出现寄生虫血症的冈比亚儿童,通过对3个多态性位点——裂殖子表面蛋白1分子(msp1)第2重复区域、msp2重复区域以及富含谷氨酸蛋白基因(glurp)的R11区域进行聚合酶链反应分析确定,其可检测到的恶性疟原虫基因型明显少于对照儿童。msp1、msp2和glurp的基因型几何平均数分别为1.66对1.87、1.95对2.43和1.21对1.50(P = 0.31、P = 0.04和P < 0.01)。排除有症状疟疾患儿后,msp1和msp2的组间差异变得更为明显。在msp1分子11个氨基酸序列中第44和47位氨基酸等位基因的流行率方面,从接种SPf66疫苗儿童或对照儿童获得的寄生虫之间未发现显著差异,msp1分子存在于SPf66中。观察到的基因型数量减少无法用接种SPf66疫苗儿童和对照儿童之间的寄生虫密度差异来解释,因为两组的寄生虫几何平均密度几乎相同。这些观察结果表明,SPf66疫苗可能诱导了一种免疫反应,该反应降低了免疫儿童新感染的发生率或加速了个体基因型寄生虫的清除率。然而,接种SPf66疫苗的儿童未记录到寄生虫血症患病率或密度的降低,这表明存在某种控制低水平疟疾寄生虫血症的密度依赖性机制。

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