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Structure-based approaches to antigen design utilize insights from antibody (Ab):antigen interactions and a refined understanding of protective Ab responses to engineer novel antigens presenting epitopes with conformations relevant to eliciting or discovering protective humoral responses. For human immunodeficiency virus-1 (HIV-1), one model of protection is provided by broadly neutralizing Abs (bnAbs) against epitopes present in the closed prefusion trimeric conformation of HIV-1 envelope glycoprotein, such as the variable loops 1-2 (V1V2) apex. Here, computational design and directed evolution yielded a novel V1V2 sequence variant with potential utility for inclusion in an immunogen for eliciting bnAbs, or as an epitope probe for their detection. The computational design goal was to engineer a minimal single-chain antigen with three copies of the V1V2 loops to support maintenance of closed prefusion V1V2 trimeric conformation and presentation of bnAb epitopes. Via directed evolution of this computationally designed single-chain antigen, we isolated a V1V2 sequence variant that in monomeric form exhibited preferential recognition by quaternary-preferring and conformation-dependent mAbs. Structural context and transferability of this phenotype to V1V2 sequences from all strains of HIV-1 tested suggest a conformation-stabilizing effect. This example demonstrates the potential utility of computational design and directed evolution-based protein engineering strategies to develop minimal, conformation-stabilized epitope-specific antigens.
Pubmed ID: 29897567
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A commercial antibody supplier and provider of various services.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsSoftware that eliminates poorly aligned positions and divergent regions of a DNA or protein alignment so that it becomes more suitable for phylogenetic analysis.
View all literature mentionsNIH HIV Reagent Program has been managed under contract by American Type Culture Collection (ATCC) since 2020. ATCC shall maintain the NIH HIV Reagent Program through identification, acquisition, production, receipt, storage, maintenance, distribution and disposal of biological and chemical research organisms and materials for HIV and other infectious diseases for use in basic and translational research.
View all literature mentionsCell line HEK293-F is a Transformed cell line with a species of origin Homo sapiens (Human)
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