Abstract
Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- AIDS Vaccines / immunology*
- Africa South of the Sahara
- Antibodies, Monoclonal / immunology*
- B-Lymphocyte Subsets / immunology
- Epitopes / immunology
- HIV Antibodies / biosynthesis
- HIV Antibodies / immunology*
- HIV Envelope Protein gp120 / chemistry
- HIV Envelope Protein gp120 / immunology*
- HIV Envelope Protein gp41 / immunology
- HIV Infections / immunology*
- HIV-1 / immunology*
- Humans
- Immunologic Memory
- Lymphocyte Activation
- Neutralization Tests
- Peptide Fragments / immunology
- Protein Multimerization
- Recombinant Proteins / immunology
Substances
- AIDS Vaccines
- Antibodies, Monoclonal
- Epitopes
- HIV Antibodies
- HIV Envelope Protein gp120
- HIV Envelope Protein gp41
- HIV envelope protein gp120 (305-321)
- Peptide Fragments
- Recombinant Proteins
- gp120 protein, Human immunodeficiency virus 1
- gp41 protein, Human immunodeficiency virus 1