+検索条件
-Structure paper
タイトル | Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance. |
---|---|
ジャーナル・号・ページ | Cell, Vol. 177, Issue 5, Page 1153-1171.e28, Year 2019 |
掲載日 | 2019年5月16日 |
著者 | 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 / |
PubMed 要旨 | 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 ...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 (T) 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-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes. |
リンク | Cell / PubMed:31080066 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 16.4 - 29.5 Å |
構造データ | EMDB-0569: EMDB-0570: EMDB-0571: EMDB-0572: EMDB-0573: EMDB-0574: EMDB-0575: EMDB-0576: EMDB-0577: EMDB-0578: EMDB-0579: EMDB-0580: EMDB-0581: EMDB-0582: EMDB-9138: EMDB-9175: EMDB-9176: EMDB-9177: EMDB-9178: EMDB-9179: EMDB-9180: EMDB-9181: EMDB-9182: EMDB-9183: EMDB-9184: EMDB-9185: EMDB-9186: |
由来 |
|