Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target

• Published in: Science (American Association for the Advancement of Science) Vol. 326; no. 5950; pp. 285 - 289
• Main Authors: Walker, Laura M, Phogat, Sanjay K, Chan-Hui, Po-Ying, Wagner, Denise, Phung, Pham, Goss, Julie L, Wrin, Terri, Simek, Melissa D, Fling, Steven, Mitcham, Jennifer L, Lehrman, Jennifer K, Priddy, Frances H, Olsen, Ole A, Frey, Steven M, Hammond, Phillip W, Kaminsky, Stephen, Zamb, Timothy, Moyle, Matthew, Koff, Wayne C, Poignard, Pascal, Burton, Dennis R
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 09.10.2009; The American Association for the Advancement of Science
• Subjects: Africa South of the Sahara; AIDS Vaccines - immunology; Antibodies; Antibodies, Monoclonal - immunology; Antigens; B lymphocytes; B-Lymphocyte Subsets - immunology; Biological and medical sciences; Cell culture; Cellular biology; Cultured cells; Epitopes; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; 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; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunologic Memory; Immunology; Infectious diseases; Lymphocyte Activation; Medical sciences; Microbiology; Neutralization Tests; Neutralizing antibodies; Peptide Fragments - immunology; Protein Multimerization; Proteins; Recombinant Proteins - immunology; Trimers; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Viruses; Africa South of the Sahara; Human; Immunopathology; Antigenic determinant; HIV-1 virus; Antibody; Retroviridae; AIDS; Vaccine; Immune deficiency; Lentivirus; Neutralizing antibody; Infection; Virus; Viral disease; Human immunodeficiency virus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1178746

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.