Dataset Information


Intra-spike crosslinking overcomes antibody evasion by HIV-1.

ABSTRACT: Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV's low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a "molecular ruler" to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders of magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection.


PROVIDER: S-EPMC4401576 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC3271928 | BioStudies
2009-01-01 | S-EPMC2678646 | BioStudies
2020-01-01 | S-EPMC7311918 | BioStudies
2020-01-01 | S-EPMC7302198 | BioStudies
2012-01-01 | S-EPMC7120587 | BioStudies
2010-01-01 | S-EPMC3699875 | BioStudies
2009-01-01 | S-EPMC2772785 | BioStudies
2017-01-01 | S-EPMC5533903 | BioStudies
2015-01-01 | S-EPMC4468504 | BioStudies
2021-01-01 | S-EPMC7924862 | BioStudies