Characterization of a vaccine-elicited human antibody with sequence homology to VRC01-class antibodies that binds the C1C2 gp120 domain

被引：1

作者：

Gray, Matthew D. ^{[1
]}

Feng, Junli ^{[1
]}

Weidle, Connor E. ^{[1
,6
]}

Cohen, Kristen W. ^{[1
]}

Ballweber-Fleming, Lamar ^{[1
]}

MacCamy, Anna J. ^{[1
]}

Huynh, Crystal N. ^{[1
]}

Trichka, Josephine J. ^{[1
,7
]}

Montefiori, David ^{[2
]}

Ferrari, Guido ^{[2
]}

Pancera, Marie ^{[1
,3
]}

McElrath, M. Juliana ^{[1
,4
,5
]}

Stamatatos, Leonidas ^{[1
,4
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[2] Duke Human Vaccine Inst, Durham, NC 27710 USA

[3] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[4] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

[5] Univ Washington, Dept Med, Seattle, WA 98195 USA

[6] Ozette Technol, 18 W Mercer St, Seattle, WA 98119 USA

[7] Case Western Reserve Univ, Sch Med, Dept Pathol, Iris S & Bert L Wolstein Res Bldg,2103 Cornell Rd, Cleveland, OH 44106 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 18期

关键词：

BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODY; B-CELL RECEPTORS; ENVELOPE PROTEIN; HIV; CYTOTOXICITY; MATURATION; EPITOPE; IDENTIFICATION; IMMUNOGENS;

D O I：

10.1126/sciadv.abm3948

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Broadly HIV-1-neutralizing VRC01-class antibodies bind the CD4-binding site of Env and contain V(H)1-2*02-derived heavy chains paired with light chains expressing five-amino acid-long CDRL3s. Their unmutated germline forms do not recognize HIV-1 Env, and their lack of elicitation in human clinical trials could be due to the absence of activation of the corresponding naive B cells by the vaccine immunogens. To address this point, we examined Env-specific B cell receptor sequences from participants in the HVTN 100 clinical trial. Of all the sequences analyzed, only one displayed homology to VRC01-class antibodies, but the corresponding antibody (FH1) recognized the C1C2 gp120 domain. For FH1 to switch epitope recognition to the CD4-binding site, alterations in the CDRH3 and CDRL3 were necessary. Only germ line-targeting Env immunogens efficiently activated VRC01 B cells, even in the presence of FH1 B cells. Our findings support the use of these immunogens to activate VRC01 B cells in humans.

引用

页数：10

共 59 条

[1] Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens [J].

Abbott, Robert K. ;

Lee, Jeong Hyun ;

Menis, Sergey ;

Skog, Patrick ;

Rossi, Meghan ;

Ota, Takayuki ;

Kulp, Daniel W. ;

Bhullar, Deepika ;

Kalyuzhniy, Oleksandr ;

Havenar-Daughton, Colin ;

Schief, William R. ;

Nemazee, David ;

Crotty, Shane .

IMMUNITY, 2018, 48 (01) :133-+

[2] Structural Definition of an Antibody-Dependent Cellular Cytotoxicity Response Implicated in Reduced Risk for HIV-1 Infection [J].

Acharya, Priyamvada ;

Tolbert, William D. ;

Gohain, Neelakshi ;

Wu, Xueji ;

Yu, Lei ;

Liu, Tongyun ;

Huang, Wensheng ;

Huang, Chih-chin ;

Do Kwon, Young ;

Louder, Robert K. ;

Luongo, Timothy S. ;

McLellan, Jason S. ;

Pancera, Marie ;

Yang, Yongping ;

Zhang, Baoshan ;

Flinko, Robin ;

Foulke, James S., Jr. ;

Sajadi, Mohammad M. ;

Kamin-Lewis, Roberta ;

Robinson, James E. ;

Martin, Loic ;

Kwong, Peter D. ;

Guan, Yongjun ;

DeVico, Anthony L. ;

Lewis, George K. ;

Pazgier, Marzena .

JOURNAL OF VIROLOGY, 2014, 88 (21) :12895-12906

[3] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[4] Antibody-based protection against HIV infection by vectored immunoprophylaxis [J].

Balazs, Alejandro B. ;

Chen, Joyce ;

Hong, Christin M. ;

Rao, Dinesh S. ;

Yang, Lili ;

Baltimore, David .

NATURE, 2012, 481 (7379) :81-U88

[5] Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial [J].

Bekker, Linda-Gail ;

Moodie, Zoe ;

Grunenberg, Nicole ;

Laher, Fatima ;

Tomaras, Georgia D. ;

Cohen, Kristen W. ;

Allen, Mary ;

Malahleha, Mookho ;

Mngadi, Kathryn ;

Daniels, Brodie ;

Innes, Craig ;

Bentley, Carter ;

Frahm, Nicole ;

Morris, Daryl E. ;

Morris, Lynn ;

Mkhize, Nonhlanhla N. ;

Montefiori, David C. ;

Sarzotti-Kelsoe, Marcella ;

Grant, Shannon ;

Yu, Chenchen ;

Mehra, Vijay L. ;

Pensiero, Michael N. ;

Phogat, Sanjay ;

DiazGranados, Carlos A. ;

Barnett, Susan W. ;

Kanesa-thasan, Niranjan ;

Koutsoukos, Marguerite ;

Michael, Nelson L. ;

Robb, Merlin L. ;

Kublin, James G. ;

Gilbert, Peter B. ;

Corey, Lawrence ;

Gray, Glenda E. ;

McElrath, M. Juliana .

LANCET HIV, 2018, 5 (07) :E366-E378

[6] Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family [J].

Bonsignori, Mattia ;

Pollara, Justin ;

Moody, M. Anthony ;

Alpert, Michael D. ;

Chen, Xi ;

Hwang, Kwan-Ki ;

Gilbert, Peter B. ;

Huang, Ying ;

Gurley, Thaddeus C. ;

Kozink, Daniel M. ;

Marshall, Dawn J. ;

Whitesides, John F. ;

Tsao, Chun-Yen ;

Kaewkungwal, Jaranit ;

Nitayaphan, Sorachai ;

Pitisuttithum, Punnee ;

Rerks-Ngarm, Supachai ;

Kim, Jerome H. ;

Michael, Nelson L. ;

Tomaras, Georgia D. ;

Montefiori, David C. ;

Lewis, George K. ;

DeVico, Anthony ;

Evans, David T. ;

Ferrari, Guido ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2012, 86 (21) :11521-11532

[7] Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors [J].

Bonsignori, Mattia ;

Hwang, Kwan-Ki ;

Chen, Xi ;

Tsao, Chun-Yen ;

Morris, Lynn ;

Gray, Elin ;

Marshall, Dawn J. ;

Crump, John A. ;

Kapiga, Saidi H. ;

Sam, Noel E. ;

Sinangil, Faruk ;

Pancera, Marie ;

Yang Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Kwong, Peter D. ;

O'Dell, Sijy ;

Mascola, John R. ;

Wu, Lan ;

Nabel, Gary J. ;

Phogat, Sanjay ;

Seaman, Michael S. ;

Whitesides, John F. ;

Moody, M. Anthony ;

Kelsoe, Garnett ;

Yang, Xinzhen ;

Sodroski, Joseph ;

Shaw, George M. ;

Montefiori, David C. ;

Kepler, Thomas B. ;

Tomaras, Georgia D. ;

Alam, S. Munir ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2011, 85 (19) :9998-10009

[8] Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies [J].

Briney, Bryan ;

Sok, Devin ;

Jardine, Joseph G. ;

Kulp, Daniel W. ;

Skog, Patrick ;

Menis, Sergey ;

Jacak, Ronald ;

Kalyuzhniy, Oleksandr ;

de Val, Natalia ;

Sesterhenn, Fabian ;

Le, Khoa M. ;

Ramos, Alejandra ;

Jones, Meaghan ;

Saye-Francisco, Karen L. ;

Blane, Tanya R. ;

Spencer, Skye ;

Georgeson, Erik ;

Hu, Xiaozhen ;

Ozorowski, Gabriel ;

Adachi, Yumiko ;

Kubitz, Michael ;

Sarkar, Anita ;

Wilson, Ian A. ;

Ward, Andrew B. ;

Nemazee, David ;

Burton, Dennis R. ;

Schief, William R. .

CELL, 2016, 166 (06) :1459-+

[9] Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design [J].

Burton, Dennis R. ;

Hangartner, Lars .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 34, 2016, 34 :635-659

[10]

Chua J. V., VACCINE, V39

← 1 2 3 4 5 6 →