作者
Kimberly M Cirelli, Diane G Carnathan, Bartek Nogal, Jacob T Martin, Oscar L Rodriguez, Amit A Upadhyay, Chiamaka A Enemuo, Etse H Gebru, Yury Choe, Federico Viviano, Catherine Nakao, Matthias G Pauthner, Samantha Reiss, Christopher A Cottrell, Melissa L Smith, Raiza Bastidas, William Gibson, Amber N Wolabaugh, Mariane B Melo, Benjamin Cossette, Venkatesh Kumar, Nirav B Patel, Talar Tokatlian, Sergey Menis, Daniel W Kulp, Dennis R Burton, Ben Murrell, William R Schief, Steven E Bosinger, Andrew B Ward, Corey T Watson, Guido Silvestri, Darrell J Irvine, Shane Crotty
发表日期
2019/5/16
期刊
Cell
卷号
177
期号
5
页码范围
1153-1171. e28
出版商
Cell Press
简介
Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery …
引用总数
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