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...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017
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| Subjects: | |
| Online Access: | http://eprints.sunway.edu.my/496/1/VRC38%20main%20text%20final%20JMB_EMC.pdf http://eprints.sunway.edu.my/496/ https://doi.org/10.1016/j.immuni.2017.04.011 |
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| Institution: | Sunway University |
| Language: | English |
| Summary: | 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. |
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