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TitleLong-primed germinal centres with enduring affinity maturation and clonal migration.
Journal, issue, pagesNature, Vol. 609, Issue 7929, Page 998-991004, Year 2022
Publish dateSep 21, 2022
AuthorsJeong Hyun Lee / Henry J Sutton / Christopher A Cottrell / Ivy Phung / Gabriel Ozorowski / Leigh M Sewall / Rebecca Nedellec / Catherine Nakao / Murillo Silva / Sara T Richey / Jonathan L Torres / Wen-Hsin Lee / Erik Georgeson / Michael Kubitz / Sam Hodges / Tina-Marie Mullen / Yumiko Adachi / Kimberly M Cirelli / Amitinder Kaur / Carolina Allers / Marissa Fahlberg / Brooke F Grasperge / Jason P Dufour / Faith Schiro / Pyone P Aye / Oleksandr Kalyuzhniy / Alessia Liguori / Diane G Carnathan / Guido Silvestri / Xiaoying Shen / David C Montefiori / Ronald S Veazey / Andrew B Ward / Lars Hangartner / Dennis R Burton / Darrell J Irvine / William R Schief / Shane Crotty /
PubMed AbstractGerminal centres are the engines of antibody evolution. Here, using human immunodeficiency virus (HIV) Env protein immunogen priming in rhesus monkeys followed by a long period without further ...Germinal centres are the engines of antibody evolution. Here, using human immunodeficiency virus (HIV) Env protein immunogen priming in rhesus monkeys followed by a long period without further immunization, we demonstrate germinal centre B (B) cells that last for at least 6 months. A 186-fold increase in B cells was present by week 10 compared with conventional immunization. Single-cell transcriptional profiling showed that both light- and dark-zone germinal centre states were sustained. Antibody somatic hypermutation of B cells continued to accumulate throughout the 29-week priming period, with evidence of selective pressure. Env-binding B cells were still 49-fold above baseline at 29 weeks, which suggests that they could remain active for even longer periods of time. High titres of HIV-neutralizing antibodies were generated after a single booster immunization. Fully glycosylated HIV trimer protein is a complex antigen, posing considerable immunodominance challenges for B cells. Memory B cells generated under these long priming conditions had higher levels of antibody somatic hypermutation, and both memory B cells and antibodies were more likely to recognize non-immunodominant epitopes. Numerous B cell lineage phylogenies spanning more than the 6-month germinal centre period were identified, demonstrating continuous germinal centre activity and selection for at least 191 days with no further antigen exposure. A long-prime, slow-delivery (12 days) immunization approach holds promise for difficult vaccine targets and suggests that patience can have great value for tuning of germinal centres to maximize antibody responses.
External linksNature / PubMed:36131022 / PubMed Central
MethodsEM (single particle)
Resolution25.0 Å
Structure data

EMDB-27600: BG505 MD39 SOSIP in complex with Rh.L614 wk13 base, N335/N289, V5/C3 and N611 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27601: BG505 MD39 SOSIP in complex with Rh.K409 wk13 base, FP/gp41, V5/C3 and N611 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27602: BG505 MD39 SOSIP in complex with Rh.K487 wk13 base, FP/gp41, and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27603: BG505 MD39 SOSIP in complex with Rh.DGT5 wk13 base, N335/N289, V1/V3 and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27604: BG505 MD39 SOSIP in complex with Rh.K949 wk33 base, N335/N289, V1/V3, N611 and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27605: BG505 MD39 SOSIP in complex with Rh.L282 wk33 base, N335/N289, FP/gp41 and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27607: BG505 MD39 SOSIP in complex with Rh.DHHT wk33 base, FP/gp41 and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27608: BG505 MD39 SOSIP in complex with Rh.DHID wk33 base, N355/N289 and V1/V3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27609: BG505 MD39 SOSIP in complex with Rh.NJ78 wk13 V5/C3 and base epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27610: BG505 MD39 SOSIP in complex with Rh.NJ82 wk13 N611 and base epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27611: BG505 MD39 SOSIP in complex with Rh.NJ95 wk13 base epitope pAb
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27612: BG505 MD39 SOSIP in complex with Rh.NK05 wk13 base epitope pAb
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27614: BG505 MD39 SOSIP in complex with Rh.NJ79 wk13 base epitope pAb
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-27615: BG505 MD39 SOSIP in complex with Rh.NJ93 wk13 base and V5/C3 epitope pAbs
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • Macaca mulatta (Rhesus monkey)
  • Human immunodeficiency virus 1

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