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TitleSlow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.
Journal, issue, pagesCell, Vol. 177, Issue 5, Page 1153-1171.e28, Year 2019
Publish dateMay 16, 2019
AuthorsKimberly 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 AbstractConventional 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.
External linksCell / PubMed:31080066 / PubMed Central
MethodsEM (single particle)
Resolution16.4 - 29.5 Å
Structure data

EMDB-0569:
HIV-1 vaccine elicited polyclonal 5N6 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 19.6 Å

EMDB-0570:
HIV-1 vaccine elicited polyclonal 99-13 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-0571:
HIV-1 vaccine elicited polyclonal 145-11 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 18.45 Å

EMDB-0572:
HIV-1 vaccine elicited polyclonal BM57 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-0573:
HIV-1 vaccine elicited polyclonal BO77 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 18.45 Å

EMDB-0574:
HIV-1 vaccine elicited polyclonal BO77 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 19.6 Å

EMDB-0575:
HIV-1 vaccine elicited polyclonal RAa14 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 19.7 Å

EMDB-0576:
HIV-1 vaccine elicited polyclonal RAv16 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 29.5 Å

EMDB-0577:
HIV-1 vaccine elicited polyclonal RAv16 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 26.38 Å

EMDB-0578:
HIV-1 vaccine elicited polyclonal REj15 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-0579:
HIV-1 vaccine elicited polyclonal REv16 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-0580:
HIV-1 vaccine elicited polyclonal RHw16 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 18.45 Å

EMDB-0581:
HIV-1 vaccine elicited polyclonal RMI15 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 22.7 Å

EMDB-0582:
HIV-1 vaccine elicited polyclonal RWo16 Fab in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-9138:
HIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trimer BG505 SOSIPv5.2
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-9175:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate 224-13
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9176:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RCn
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9177:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RFr16
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9178:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate ROw16
Method: EM (single particle) / Resolution: 24.6 Å

EMDB-9179:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RQq16
Method: EM (single particle) / Resolution: 29.5 Å

EMDB-9180:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RRk16
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-9181:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RVh16
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9182:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RTh16
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9183:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RWh16
Method: EM (single particle) / Resolution: 26.8 Å

EMDB-9184:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RWr16
Method: EM (single particle) / Resolution: 24.5 Å

EMDB-9185:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate RYm16
Method: EM (single particle) / Resolution: 16.4 Å

EMDB-9186:
Negative Stain EM map of polyclonal serum in complex with BG505 SOSIP.664 from non-human primate ROw16
Method: EM (single particle) / Resolution: 24.5 Å

Source
  • Homo sapiens (human)
  • Macaca (macaques)
  • Human immunodeficiency virus 1
  • Macaca mulatta (Rhesus monkey)

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