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沙发
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发表于 2016-3-31 14:20:46
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HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen
Joseph G. Jardine1,2,3,*, Daniel W. Kulp1,2,3,*, Colin Havenar-Daughton3,4,*, Anita Sarkar2,3,5,*, Bryan Briney1,2,3,*, Devin Sok1,2,3,*, Fabian Sesterhenn1,†, June Ereño-Orbea6, Oleksandr Kalyuzhniy1,2,3, Isaiah Deresa3,4, Xiaozhen Hu1,3, Skye Spencer1,3, Meaghan Jones1,3, Erik Georgeson1,3, Yumiko Adachi1,2,3, Michael Kubitz1,2,3, Allan C. deCamp7, Jean-Philippe Julien2,3,5,6,8, Ian A. Wilson2,3,5,9, Dennis R. Burton1,2,3,10, Shane Crotty3,4,11,‡, William R. Schief
Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.
http://science.sciencemag.org/content/351/6280/1458 |
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