Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody
Copyright policy )Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
- University of Amsterdam Netherlands
- Harvard University United States
- California Institute of Technology United States
- German Center for Infection Research Germany
- Cornell University United States
Male, 610, HIV Infections, CHO Cells, HIV Antibodies, CD4 binding site, Article, Cohort Studies, Epitopes, Mice, Cricetulus, deep mutational scanning, Mice, Inbred NOD, Animals, Humans, ddc:610, Binding Sites, cryogenic electron microscopy, broadly neutralizing antibodies, HIV-1 escape restriction, Antibodies, Monoclonal, Middle Aged, escape mutations, humanized mice, HEK293 Cells, CD4 Antigens, mutational antigenic profiling, HIV-1, Heterografts, Female, immunotherapy, Broadly Neutralizing Antibodies, ddc: ddc:610
Male, 610, HIV Infections, CHO Cells, HIV Antibodies, CD4 binding site, Article, Cohort Studies, Epitopes, Mice, Cricetulus, deep mutational scanning, Mice, Inbred NOD, Animals, Humans, ddc:610, Binding Sites, cryogenic electron microscopy, broadly neutralizing antibodies, HIV-1 escape restriction, Antibodies, Monoclonal, Middle Aged, escape mutations, humanized mice, HEK293 Cells, CD4 Antigens, mutational antigenic profiling, HIV-1, Heterografts, Female, immunotherapy, Broadly Neutralizing Antibodies, ddc: ddc:610
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