Abstract
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
Publication types
-
Research Support, N.I.H., Intramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AIDS Vaccines
-
Antibodies, Monoclonal / immunology*
-
Antibodies, Monoclonal / isolation & purification
-
Antibodies, Neutralizing / immunology*
-
Antibodies, Neutralizing / isolation & purification
-
Antibody Specificity
-
B-Lymphocytes / immunology
-
Binding Sites, Antibody
-
CD4 Antigens / immunology
-
CD4 Antigens / metabolism
-
Cross Reactions
-
Drug Design
-
Enzyme-Linked Immunosorbent Assay
-
Epitopes / immunology
-
Genes, Immunoglobulin Heavy Chain
-
Genes, Immunoglobulin Light Chain
-
HIV Antibodies / immunology*
-
HIV Antibodies / isolation & purification
-
HIV Envelope Protein gp120 / chemistry
-
HIV Envelope Protein gp120 / immunology*
-
HIV Envelope Protein gp120 / metabolism
-
HIV Infections / immunology
-
HIV Infections / virology
-
HIV-1 / genetics
-
HIV-1 / immunology*
-
Humans
-
Molecular Sequence Data
-
Neutralization Tests
-
Protein Engineering
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / immunology
-
Recombinant Proteins / metabolism
Substances
-
AIDS Vaccines
-
Antibodies, Monoclonal
-
Antibodies, Neutralizing
-
CD4 Antigens
-
Epitopes
-
HIV Antibodies
-
HIV Envelope Protein gp120
-
Recombinant Proteins
Associated data
-
GENBANK/GU980702
-
GENBANK/GU980703
-
GENBANK/GU980704
-
GENBANK/GU980705
-
GENBANK/GU980706
-
GENBANK/GU980707