Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization

• Published in: Science (American Association for the Advancement of Science) Vol. 340; no. 6133; pp. 751 - 756
• Main Authors: Georgiev, Ivelin S., Doria-Rose, Nicole A., Zhou, Tongqing, Kwon, Young Do, Staupe, Ryan P., Moquin, Stephanie, Chuang, Gwo-Yu, Louder, Mark K., Schmidt, Stephen D., Altae-Tran, Han R., Bailer, Robert T., McKee, Krisha, Nason, Martha, O'Dell, Sijy, Ofek, Gilad, Pancera, Marie, Srivatsan, Sanjay, Shapiro, Lawrence, Connors, Mark, Migueles, Stephen A., Morris, Lynn, Nishimura, Yoshiaki, Martin, Malcolm A., Mascola, John R., Kwong, Peter D.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 10.05.2013; The American Association for the Advancement of Science
• Subjects: Algorithms; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibody specificity; Design analysis; Envelopes; Epitope Mapping; Epitopes; germ cells; HIV; HIV 1; HIV Antibodies - blood; HIV Antibodies - immunology; HIV infections; HIV Infections - blood; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune response; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - immunology; Immunoglobulins; Macaca; Monoclonal antibodies; Neutralization; Neutralization Tests; Neutralizing; Neutralizing antibodies; patients; Pattern recognition; Pharmaceutical sciences; Polyclonal antibodies; Precursors; Protein Conformation; Proteins; screening; Serum - immunology; Signals; Vaccination; vaccine development; Vaccines; viral envelope proteins; Viruses
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1233989

Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.