Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop
Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, enabl them to penetrate the HIV-1 glycan shie...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017
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| Online Access: | http://eprints.sunway.edu.my/496/ http://eprints.sunway.edu.my/496/1/VRC38%20main%20text%20final%20JMB_EMC.pdf |
| _version_ | 1848801832969699328 |
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| author | Cale, Evan M Gorman, Jason Radakovich, Nathan A Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * |
| author_facet | Cale, Evan M Gorman, Jason Radakovich, Nathan A Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * |
| author_sort | Cale, Evan M |
| building | SU Institutional Repository |
| collection | Online Access |
| description | Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, enabl them to penetrate the HIV-1
glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain to side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, facilitating V1V2
binding via a non-protruding loop. The N90-VRC38 lineage identifies a solution for V1V2apex binding that provides a more conventional B cell pathway for vaccine design. |
| first_indexed | 2025-11-14T21:13:44Z |
| format | Article |
| id | sunway-496 |
| institution | Sunway University |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:13:44Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-4962020-01-23T03:34:52Z http://eprints.sunway.edu.my/496/ Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop Cale, Evan M Gorman, Jason Radakovich, Nathan A Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * QR Microbiology QR180 Immunology Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, enabl them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain to side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage identifies a solution for V1V2apex binding that provides a more conventional B cell pathway for vaccine design. Elsevier 2017-05-16 Article PeerReviewed text en cc_by_nc_nd http://eprints.sunway.edu.my/496/1/VRC38%20main%20text%20final%20JMB_EMC.pdf Cale, Evan M and Gorman, Jason and Radakovich, Nathan A and Crooks, Ema T and Osawa, Keiko and Tong, Tommy Yuh Koon * (2017) Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop. Immunity, 46 (5 ). pp. 777-791. https://doi.org/10.1016/j.immuni.2017.04.011 10.1016/j.immuni.2017.04.011. |
| spellingShingle | QR Microbiology QR180 Immunology Cale, Evan M Gorman, Jason Radakovich, Nathan A Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title | Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title_full | Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title_fullStr | Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title_full_unstemmed | Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title_short | Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop |
| title_sort | virus-like particles identify an hiv v1v2 apex-1 binding neutralizing antibody that lacks a protruding loop |
| topic | QR Microbiology QR180 Immunology |
| url | http://eprints.sunway.edu.my/496/ http://eprints.sunway.edu.my/496/ http://eprints.sunway.edu.my/496/ http://eprints.sunway.edu.my/496/1/VRC38%20main%20text%20final%20JMB_EMC.pdf |