EMD-9177
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RFr16
EMD-9177
Single-particle26.8 Å
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Map released: 05/06/2019
Last modified: 05/06/2019
Sample Organism:
Macaca
Sample: Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RFr16
Deposition Authors: Nogal B, Ward AB
Sample: Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RFr16
Deposition Authors: Nogal B, Ward AB
Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.
Cirelli KM,
Carnathan DG,
Nogal B,
Martin JT
,
Rodriguez OL,
Upadhyay AA
,
Enemuo CA,
Gebru EH,
Choe Y,
Viviano F,
Nakao C,
Pauthner MG
,
Reiss S,
Cottrell CA,
Smith ML,
Bastidas R,
Gibson W,
Wolabaugh AN,
Melo MB,
Cossette B,
Kumar V,
Patel NB,
Tokatlian T,
Menis S,
Kulp DW,
Burton DR,
Murrell B
,
Schief WR,
Bosinger SE,
Ward AB,
Watson CT,
Silvestri G,
Irvine DJ,
Crotty S
(2019) Cell , 177 , 1153 - 1171.e28
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(2019) Cell , 177 , 1153 - 1171.e28
Abstract:
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-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.
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-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.