E-viri
Recenzirano
Odprti dostop
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Kulp, Daniel W; Steichen, Jon M; Pauthner, Matthias; Hu, Xiaozhen; Schiffner, Torben; Liguori, Alessia; Cottrell, Christopher A; Havenar-Daughton, Colin; Ozorowski, Gabriel; Georgeson, Erik; Kalyuzhniy, Oleksandr; Willis, Jordan R; Kubitz, Michael; Adachi, Yumiko; Reiss, Samantha M; Shin, Mia; de Val, Natalia; Ward, Andrew B; Crotty, Shane; Burton, Dennis R; Schief, William R
Nature communications, 11/2017, Letnik: 8, Številka: 1Journal Article
Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity. In rabbit immunizations with native-like trimers of the 327c isolate, improved trimers suppress elicitation of V3-directed and tier-1 neutralizing antibodies and induce robust autologous tier-2 neutralization, unlike a first-generation trimer. The improved native-like trimers from diverse HIV isolates, and the design methods, have promise to assist in the development of a HIV vaccine.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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