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Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.

Sci Transl Med. 2016; 
Zhang Ruijun,Verkoczy Laurent,Wiehe Kevin,Munir Alam S,Nicely Nathan I,Santra Sampa,Bradley Todd,Pemble Charles W,Zhang Jinsong,Gao Feng,Montefiori David C,Bouton-Verville Hilary,Kelsoe Garnett,Larimore Kevin,Greenberg Phillip D,Parks Robert,Foulger Andrew,Peel Jessica N,Luo Kan,Lu Xiaozhi,Trama Ashley M,Vandergrift Nathan,Tomaras Georgia D,Kepler Thomas B,Moody M Anthony,Liao Hua-Xin,Haynes Bart
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摘要

Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either ... More

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