Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target

LM Walker, SK Phogat, PY Chan-Hui, D Wagner… - Science, 2009 - science.org
LM Walker, SK Phogat, PY Chan-Hui, D Wagner, P Phung, JL Goss, T Wrin, MD Simek…
Science, 2009science.org
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 …
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.
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