Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds.
Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds.
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DOI：
10.1016/j.chembiol.2010.03.012
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发表时间：
2010-04-23
影响因子：
--
通讯作者：
Burton DR
中科院分区：
文献类型：
--
作者：
Astronomo RD;Kaltgrad E;Udit AK;Wang SK;Doores KJ;Huang CY;Pantophlet R;Paulson JC;Wong CH;Finn MG;Burton DR
广泛中和的抗体2G12识别了HIV表面包膜突突上的一个保守的高甘露糖聚糖簇，这表明病毒的“聚糖屏蔽”防御可以被破坏，并且在适当的情况下，可以作为疫苗靶标。为了半合成重现聚糖屏蔽的特征，我们在噬菌体Qβ和豇豆花叶病毒（CPMV）的二十面体衣壳上偶联了寡糖甘露苷和表面赖氨酸。Qβ糖缀合物，而不是CPMV，呈现高亲和力结合抗体2G12的寡甘露糖簇。然而，在免疫家兔中未检测到针对这些2G12表位的抗体。相反，偶联物上的其他寡甘露糖表位具有免疫优势，并引发不与HIV包膜交叉反应的高滴度抗甘露糖抗体。提出的结果揭示了以碳水化合物为基础的HIV疫苗成分的重要设计考虑因素。
The broadly neutralizing antibody 2G12 recognizes a conserved cluster of high mannose glycans on the surface envelope spike of HIV suggesting that the “glycan shield” defense of the virus can be breached and may, under the right circumstances, serve as a vaccine target. In an attempt to recreate features of the glycan shield semi-synthetically, oligomannosides were coupled to surface lysines on the icosahedral capsids of bacteriophage Qβ and cowpea mosaic virus (CPMV). The Qβ glycoconjugates, but not CPMV, presented oligomannose clusters that bind the antibody 2G12 with high affinity. However, Abs against these 2G12 epitopes were not detected in immunized rabbits. Rather, alternative oligomannose epitopes on the conjugates were immunodominant and elicited high titres of anti-mannose Abs that do not cross-react with the HIV envelope. The results presented reveal important design considerations for a carbohydrate-based vaccine component for HIV.
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影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
影响因子：
15
作者：
Lewis, WG;Magallon, FG;Finn, MG
通讯作者：
Finn, MG
影响因子：
5.4
作者：
Binley, James M.;Lybarger, Elizabeth A.;Mascola, John R.
通讯作者：
Mascola, John R.
影响因子：
15
作者：
Krauss, Isaac J.;Joyce, Joseph G.;Danishefsky, Samuel J.
通讯作者：
Danishefsky, Samuel J.