Antigenicity and immunogenicity of Plasmodium vivax merozoite surface protein-3.
Antigenicity and immunogenicity of Plasmodium vivax merozoite surface protein-3.
复制标题
疟原虫的抗原性和免疫原性蛋白质表面蛋白-3。
DOI：
10.1371/journal.pone.0056061
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Soares IS
中科院分区：
文献类型：
--
作者：
Bitencourt AR;Vicentin EC;Jimenez MC;Ricci R;Leite JA;Costa FT;Ferreira LC;Russell B;Nosten F;Rénia L;Galinski MR;Barnwell JW;Rodrigues MM;Soares IS
最近在非洲儿童中进行的一项临床试验证明了merozoite表面蛋白(MSP)-3作为恶性疟原虫疟疾疫苗的潜在效用。本研究评估了间日疟原虫MSP-3 （PvMSP-3）作为靶抗原在间日疟原虫引起的疟疾疫苗制剂中的应用。表达间日疟原虫MSP-3α和MSP-3β的重组蛋白以可溶性组氨酸标记的细菌融合物表达。自然感染期间的抗原性通过检测来自巴西流行地区个体的血清中的特异性抗体来评估。大部分感染者出现PvMSP-3α IgG抗体（68.2%）和至少1个代表PvMSP-3β的重组蛋白（79.1%）。尽管应答频率很高，但对这两种抗原的反应性明显低于PvMSP-1的19 kda c端区域的免疫优势表位。在小鼠中研究了重组蛋白在不同佐剂配方的存在或缺失情况下的免疫原性。在没有任何佐剂制剂的情况下，PvMSP-3β诱导了tlr4独立的体液免疫反应，而PvMSP-3α则没有。在不同佐剂（明矾、肠沙门氏菌鞭毛蛋白、CpG、Quil A、TiterMax®和不完全Freunds佐剂）和两种佐剂（明矾+鞭毛蛋白、CpG +鞭毛蛋白）的组合中检测重组抗原的免疫原性。重组PvMSP-3α和PvMSP-3β诱导出更高的抗体滴度，能够识别疟疾患者采集的间日疟原虫感染红细胞。我们的研究结果证实间日疟原虫MSP-3抗原在自然感染过程中具有免疫原性，相应的重组蛋白可能有助于阐明其疫苗潜力。
A recent clinical trial in African children demonstrated the potential utility of merozoite surface protein (MSP)-3 as a vaccine against Plasmodium falciparum malaria. The present study evaluated the use of Plasmodium vivax MSP-3 (PvMSP-3) as a target antigen in vaccine formulations against malaria caused by P. vivax. Recombinant proteins representing MSP-3α and MSP-3β of P. vivax were expressed as soluble histidine-tagged bacterial fusions. Antigenicity during natural infection was evaluated by detecting specific antibodies using sera from individuals living in endemic areas of Brazil. A large proportion of infected individuals presented IgG antibodies to PvMSP-3α (68.2%) and at least 1 recombinant protein representing PvMSP-3β (79.1%). In spite of the large responder frequency, reactivity to both antigens was significantly lower than was observed for the immunodominant epitope present on the 19-kDa C-terminal region of PvMSP-1. Immunogenicity of the recombinant proteins was studied in mice in the absence or presence of different adjuvant formulations. PvMSP-3β, but not PvMSP-3α, induced a TLR4-independent humoral immune response in the absence of any adjuvant formulation. The immunogenicity of the recombinant antigens were also tested in formulations containing different adjuvants (Alum, Salmonella enterica flagellin, CpG, Quil A,TiterMax® and incomplete Freunds adjuvant) and combinations of two adjuvants (Alum plus flagellin, and CpG plus flagellin). Recombinant PvMSP-3α and PvMSP-3β elicited higher antibody titers capable of recognizing P. vivax-infected erythrocytes harvested from malaria patients. Our results confirm that P. vivax MSP-3 antigens are immunogenic during natural infection, and the corresponding recombinant proteins may be useful in elucidating their vaccine potential.
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影响因子：
3.7
作者：
Mullen GE;Ellis RD;Miura K;Malkin E;Nolan C;Hay M;Fay MP;Saul A;Zhu D;Rausch K;Moretz S;Zhou H;Long CA;Miller LH;Treanor J
通讯作者：
Treanor J
影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
3.7
作者：
Ellis RD;Martin LB;Shaffer D;Long CA;Miura K;Fay MP;Narum DL;Zhu D;Mullen GE;Mahanty S;Miller LH;Durbin AP
通讯作者：
Durbin AP
影响因子：
3
作者：
Rodrigues, MHC;Cunha, MG;Soares, IS
通讯作者：
Soares, IS
影响因子：
1.5
作者：
Galinski, MR;Ingravallo, P;Barnwell, JW
通讯作者：
Barnwell, JW