Journal
IMMUNITY
Volume 46, Issue 5, Pages 777-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2017.04.011
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Funding
- NIH [RO1AI00790, RO1AI93278, R33AI84714, U19AI117892-02]
- Vaccine Research Center, NIAID, NIH
- US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
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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, which enable 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, by 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, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.
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