HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide
Published by Elsevier Inc..
Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
|---|---|
| Enthalten in: |
Cell reports - 42(2023), 7 vom: 25. Juli, Seite 112755 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Shuishu [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.08.2023 Date Revised 12.09.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.celrep.2023.112755 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM359377467 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM359377467 | ||
| 003 | DE-627 | ||
| 005 | 20231226210626.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2023.112755 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1197.xml |
| 035 | |a (DE-627)NLM359377467 | ||
| 035 | |a (NLM)37436899 | ||
| 035 | |a (PII)S2211-1247(23)00766-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Shuishu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.08.2023 | ||
| 500 | |a Date Revised 12.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Elsevier Inc. | ||
| 520 | |a Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a HIV vaccine | |
| 650 | 4 | |a antibody-antigen binding | |
| 650 | 4 | |a cryo-EM structure | |
| 650 | 4 | |a envelope trimer | |
| 650 | 4 | |a fusion peptide | |
| 650 | 4 | |a glycan hole | |
| 650 | 4 | |a immunogen design | |
| 650 | 4 | |a reproducible antibody class | |
| 650 | 4 | |a site of vulnerability | |
| 650 | 7 | |a AIDS Vaccines |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a env Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 650 | 7 | |a HIV Antibodies |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 700 | 1 | |a Matassoli, Flavio |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Baoshan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Tracy |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Chen-Hsiang |e verfasserin |4 aut | |
| 700 | 1 | |a Bylund, Tatsiana |e verfasserin |4 aut | |
| 700 | 1 | |a Johnston, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Henry, Amy R |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, I-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Tripathi, Prabhanshu |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Jordan E |e verfasserin |4 aut | |
| 700 | 1 | |a Changela, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Chaudhary, Ridhi |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Gaudinski, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Gorman, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Darcy R |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Myungjin |e verfasserin |4 aut | |
| 700 | 1 | |a Morano, Nicholas C |e verfasserin |4 aut | |
| 700 | 1 | |a Novik, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a O'Dell, Sijy |e verfasserin |4 aut | |
| 700 | 1 | |a Olia, Adam S |e verfasserin |4 aut | |
| 700 | 1 | |a Parchment, Danealle K |e verfasserin |4 aut | |
| 700 | 1 | |a Rawi, Reda |e verfasserin |4 aut | |
| 700 | 1 | |a Roberts-Torres, Jesmine |e verfasserin |4 aut | |
| 700 | 1 | |a Stephens, Tyler |e verfasserin |4 aut | |
| 700 | 1 | |a Tsybovsky, Yaroslav |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Danyi |e verfasserin |4 aut | |
| 700 | 1 | |a Van Wazer, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Tongqing |e verfasserin |4 aut | |
| 700 | 1 | |a Doria-Rose, Nicole A |e verfasserin |4 aut | |
| 700 | 1 | |a Koup, Richard A |e verfasserin |4 aut | |
| 700 | 1 | |a Shapiro, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Douek, Daniel C |e verfasserin |4 aut | |
| 700 | 1 | |a McDermott, Adrian B |e verfasserin |4 aut | |
| 700 | 1 | |a Kwong, Peter D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 42(2023), 7 vom: 25. Juli, Seite 112755 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
| 773 | 1 | 8 | |g volume:42 |g year:2023 |g number:7 |g day:25 |g month:07 |g pages:112755 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2023.112755 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 42 |j 2023 |e 7 |b 25 |c 07 |h 112755 | ||