Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.
Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.
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DOI：
10.1126/scitranslmed.3000257
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发表时间：
2009-10-14
影响因子：
17.1
通讯作者：
Plowe CV
中科院分区：
文献类型：
--
作者：
Takala SL;Coulibaly D;Thera MA;Batchelor AH;Cummings MP;Escalante AA;Ouattara A;Traoré K;Niangaly A;Djimdé AA;Doumbo OK;Plowe CV
针对恶性疟原虫血液阶段疟疾的疫苗旨在防止寄生虫入侵和在宿主细胞内复制。没有一种血期疟疾疫苗在人类身上显示出临床疗效。大多数疟疾疫苗抗原是寄生虫表面蛋白，已经进化出广泛的遗传多样性，这种多样性可能使疟疾寄生虫逃脱疫苗诱导的免疫。我们在马里的一项纵向研究中检查了血期疟疾疫苗抗原顶膜抗原- 1遗传多样性的程度和宿主内动态。在506例人类感染中鉴定出214种独特的根尖膜抗原- 1单倍型，在假定的入侵机制结合位点附近的氨基酸变化与临床症状的发展密切相关，这表明这些残基可能是设计多价根尖膜抗原- 1疫苗和在实地试验中评估疫苗效力时考虑的重要因素。这种极端的多样性可能对有效的多价重组亚基根尖膜抗原- 1疫苗构成严重障碍。
Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive genetic diversity, and this diversity could allow malaria parasites to escape vaccine-induced immunity. We examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine antigen apical membrane antigen–1 in a longitudinal study in Mali. Two hundred and fourteen unique apical membrane antigen–1 haplotypes were identified among 506 human infections, and amino acid changes near a putative invasion machinery binding site were strongly associated with the development of clinical symptoms, suggesting that these residues may be important to consider in designing polyvalent apical membrane antigen–1 vaccines and in assessing vaccine efficacy in field trials. This extreme diversity may pose a serious obstacle to an effective polyvalent recombinant subunit apical membrane antigen–1 vaccine.
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影响因子：
6.7
作者：
Collins, Christine R.;Withers-Martinez, Chrislaine;Hackett, Fiona;Blackman, Michael J.
通讯作者：
Blackman, Michael J.
影响因子：
3
作者：
Garg S;Alam MT;Das MK;Dev V;Kumar A;Dash AP;Sharma YD
通讯作者：
Sharma YD
DOI：
10.1073/pnas.0701464104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Dutta, Sheetij;Lee, Seung Yeon;Lanar, David E.
通讯作者：
Lanar, David E.
影响因子：
1.5
作者：
Escalante, AA;Grebert, HM;Lal, AA
通讯作者：
Lal, AA
影响因子：
1.5
作者：
Marshall, VM;Zhang, LX;Coppel, RL
通讯作者：
Coppel, RL