Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

被引：25

作者：

Williams, Wilton B. ^{[1
,2
,5
]}

Alam, S. Munir ^{[1
,4
]}

Ofek, Gilad ^{[3
,16
]}

Erdmann, Nathaniel ^{[9
]}

Montefiori, David C. ^{[1
,2
]}

Seaman, Michael S. ^{[12
]}

Wagh, Kshitij ^{[14
,15
]}

Korber, Bette ^{[14
,15
]}

Edwards, Robert J. ^{[1
,4
]}

Mansouri, Katayoun ^{[1
]}

Eaton, Amanda ^{[2
]}

Cain, Derek W. ^{[1
]}

Martin, Mitchell ^{[1
]}

Hwang, Jongin ^{[1
]}

Arus-Altuz, Aria ^{[1
]}

Lu, Xiaozhi ^{[1
]}

Cai, Fangping ^{[1
,4
]}

Jamieson, Nolan ^{[1
,4
]}

Parks, Robert ^{[1
]}

Barr, Maggie ^{[1
]}

Foulger, Andrew ^{[1
]}

Anasti, Kara ^{[1
]}

Patel, Parth ^{[1
]}

Sammour, Salam ^{[1
]}

Parsons, Ruth J. ^{[1
]}

Huang, Xiao ^{[1
]}

Lindenberger, Jared ^{[1
]}

Fetics, Susan ^{[1
]}

Janowska, Katarzyna ^{[1
]}

Niyongabo, Aurelie ^{[3
]}

Janus, Benjamin M. ^{[3
,16
]}

Astavans, Anagh ^{[3
]}

Fox, Christopher B. ^{[13
]}

Mohanty, Ipsita ^{[1
]}

Evangelous, Tyler ^{[1
]}

Chen, Yue ^{[1
]}

Berry, Madison ^{[1
]}

Kirshner, Helene ^{[1
]}

Itallie, Elizabeth Van ^{[1
]}

Saunders, Kevin O. ^{[1
,2
,5
,6
]}

Wiehe, Kevin ^{[1
,4
]}

Cohen, Kristen W. ^{[7
]}

Mcelrath, M. Juliana ^{[7
]}

Corey, Lawrence ^{[7
]}

Acharya, Priyamvada ^{[1
,2
,10
]}

Walsh, Stephen R. ^{[8
]}

Baden, Lindsey R. ^{[8
]}

Haynes, Barton F. ^{[1
,5
,11
]}

机构：

[1] Duke Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA

[2] Duke Sch Med, Dept Surg, Durham, NC 27710 USA

[3] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[4] Duke Sch Med, Dept Med, Durham, NC 27710 USA

[5] Duke Sch Med, Dept Integrat Immunobiol, Durham, NC 27710 USA

[6] Duke Sch Med, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

[7] Fred Hutchinson Canc Ctr, Seattle, WA 98109 USA

[8] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[9] Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35223 USA

[10] Duke Univ, Sch Med, Dept Biochem, Durham, NC 27710 USA

[11] Duke Sch Med, Duke Global Hlth Inst, Durham, NC 27710 USA

[12] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[13] Access Adv Hlth Inst, Seattle, WA 98102 USA

[14] Los Alamos Natl Lab, Los Alamos, NM 87545 USA

[15] New Mexico Consortium, Los Alamos, NM 87544 USA

[16] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA

来源：

CELL | 2024年 / 187卷 / 12期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; PROXIMAL EXTERNAL REGION; NEUTRALIZING HIV-1 ANTIBODY; MEMBRANE; GP41; 2F5; EPITOPE; BROAD; 4E10;

D O I：

10.1016/j.cell.2024.04.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV -1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV -1 envelope (Env) membrane -proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV -1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV -1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV -1 vaccine development.

引用

页码：2919 / 2934.e20

页数：37

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