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印度中部恰蒂斯加尔邦针对恶性疟原虫疫苗候选基因的遗传多样性及抗体反应:对疫苗开发的启示

Genetic diversity and antibody responses against Plasmodium falciparum vaccine candidate genes from Chhattisgarh, Central India: Implication for vaccine development.

作者信息

Patel Priyanka, Bharti Praveen K, Bansal Devendra, Raman Rajive K, Mohapatra Pradyumna K, Sehgal Rakesh, Mahanta Jagadish, Sultan Ali A, Singh Neeru

机构信息

National Institute for Research in Tribal Health, Indian Council of Medical Research, Garha, Jabalpur, Madhya Pradesh, India.

Department of Microbiology and Immunology, Weill Cornell Medicine - Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar.

出版信息

PLoS One. 2017 Aug 7;12(8):e0182674. doi: 10.1371/journal.pone.0182674. eCollection 2017.

Abstract

The genetic diversity in Plasmodium falciparum antigens is a major hurdle in developing an effective malaria vaccine. Protective efficacy of the vaccine is dependent on the polymorphic alleles of the vaccine candidate antigens. Therefore, we investigated the genetic diversity of the potential vaccine candidate antigens i.e. msp-1, msp-2, glurp, csp and pfs25 from field isolates of P.falciparum and determined the natural immune response against the synthetic peptide of these antigens. Genotyping was performed using Sanger method and size of alleles, multiplicity of infection, heterogeneity and recombination rate were analyzed. Asexual stage antigens were highly polymorphic with 55 and 50 unique alleles in msp-1 and msp-2 genes, respectively. The MOI for msp-1 and msp-2 were 1.67 and 1.28 respectively. A total 59 genotype was found in glurp gene with 8 types of amino acid repeats in the conserved part of RII repeat region. The number of NANP repeats from 40 to 44 was found among 55% samples in csp gene while pfs25 was found almost conserved with only two amino acid substitution site. The level of genetic diversity in the present study population was very similar to that from Asian countries. A higher IgG response was found in the B-cell epitopes of msp-1 and csp antigens and higher level of antibodies against csp B-cell epitope and glurp antigen were recorded with increasing age groups. Significantly, higher positive responses were observed in the csp antigen among the samples with ≥42 NANP repeats. The present finding showed extensive diversity in the asexual stage antigens.

摘要

恶性疟原虫抗原的遗传多样性是开发有效疟疾疫苗的主要障碍。疫苗的保护效力取决于候选疫苗抗原的多态性等位基因。因此,我们研究了潜在候选疫苗抗原,即来自恶性疟原虫野外分离株的msp-1、msp-2、glurp、csp和pfs25的遗传多样性,并确定了针对这些抗原合成肽的天然免疫反应。使用桑格法进行基因分型,并分析等位基因大小、感染复数、异质性和重组率。无性阶段抗原具有高度多态性,msp-1和msp-2基因分别有55个和50个独特等位基因。msp-1和msp-2的感染复数分别为1.67和1.28。在glurp基因中总共发现了59种基因型,在RII重复区域的保守部分有8种氨基酸重复类型。在csp基因的55%样本中发现NANP重复数为40至44,而pfs25几乎保守,只有两个氨基酸替代位点。本研究人群中的遗传多样性水平与亚洲国家的非常相似。在msp-1和csp抗原的B细胞表位中发现了较高的IgG反应,并且随着年龄组的增加,针对csp B细胞表位和glurp抗原的抗体水平升高。值得注意的是,在具有≥42个NANP重复的样本中,csp抗原的阳性反应明显更高。目前的研究结果表明无性阶段抗原具有广泛的多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba0a/5546615/0986f014e996/pone.0182674.g001.jpg

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