Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.
Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.
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由 Pfs25-EPA 纳米粒子组成的恶性疟原虫性阶段传播阻断疫苗的结构和免疫学差异。
DOI：
10.1038/s41541-023-00655-5
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发表时间：
2023-04-15
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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作者：
开发一种能够阻止不同阶段寄生虫向人类和蚊子传播的疟疾疫苗被认为是消除疟疾工作的关键。一种使用Pfs25（一种位于受精卵和卵母细胞表面的蛋白质）的疫苗正在被研究作为一种传播阻断疫苗（TBV），它将阻断寄生虫从蚊子传播到人类。研究最广泛的Pfs25 TBVs使用毕赤酵母生产的重组形式的Pfs25，化学偶联到重组载体蛋白ExoProtein a （EPA）。首次用于人类的Pfs25的重组形式被鉴定为Pfs25H，它在氨基端和羧基端含有14个异源氨基酸残基，包括一个His6亲和标签。第二个重组Pfs25，鉴定为Pfs25M，去除异源氨基酸残基并与EPA偶联（Pfs25M-EPA）。本文对单体Pfs25M进行了生物化学和生物物理表征，以确定其身份、纯度和完整性，包括蛋白质结构，以评估其与Pfs25H的可比性。尽管Pfs25H和Pfs25M的生物活性，无论是通过单体形式还是通过共轭纳米颗粒产生，看起来都是相似的，但用两种传输阻断单克隆抗体进行的精细定位研究发现了结构和免疫学上的差异。此外，在非人灵长类动物中，对共轭Pfs25H或Pfs25M纳米颗粒产生的抗血清进行评估，鉴定出识别这些结构差异的多克隆IgG。
Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences.
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影响因子：
3.7
作者：
Talaat KR;Ellis RD;Hurd J;Hentrich A;Gabriel E;Hynes NA;Rausch KM;Zhu D;Muratova O;Herrera R;Anderson C;Jones D;Aebig J;Brockley S;MacDonald NJ;Wang X;Fay MP;Healy SA;Durbin AP;Narum DL;Wu Y;Duffy PE
通讯作者：
Duffy PE
DOI：
10.1084/jem.174.5.1203
发表时间：
1991-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barr PJ;Green KM;Gibson HL;Bathurst IC;Quakyi IA;Kaslow DC
通讯作者：
Kaslow DC
影响因子：
3.2
作者：
Sookpongthai P;Utayopas K;Sitthiyotha T;Pengsakul T;Kaewthamasorn M;Wangkanont K;Harnyuttanakorn P;Chunsrivirot S;Pattaradilokrat S
通讯作者：
Pattaradilokrat S
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
15.9
作者：
Healy，Sara A.;Anderson，Charles;Duffy，Patrick E.
通讯作者：
Duffy，Patrick E.