B-cell–lineage immunogen design in vaccine development with HIV-1 as a case study

• Published in: Nature biotechnology Vol. 30; no. 5; pp. 423 - 433
• Main Authors: Haynes, Barton F, Kelsoe, Garnett, Harrison, Stephen C, Kepler, Thomas B
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.05.2012; Nature Publishing Group
• Subjects: 631/250/1619/40; 631/250/255/1901; 631/61/51/1568; 631/61/51/1868; Agriculture; AIDS vaccines; AIDS Vaccines - chemistry; Antibodies - chemistry; Antibodies, Monoclonal - chemistry; Antibody diversity; Antigens; B cells; B-Lymphocytes - cytology; Binding Sites; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Biotechnology - methods; Cell Lineage; Cell Proliferation; Chronic infection; Complementarity; Design; Dimerization; Drug Design; Epitopes; Epitopes - chemistry; Fundamental and applied biological sciences. Psychology; Genomics; Health aspects; Health. Pharmaceutical industry; HIV; HIV Antibodies - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunization; Immunogenetics; Immunology; Immunoregulation; Industrial applications and implications. Economical aspects; Life Sciences; Lymphocytes B; Monoclonal antibodies; Mutation; Neutralization Tests; Neutralizing; perspective; Physiological aspects; Product development; Production of active biomolecules; Somatic hypermutation; Vaccine development; Vaccines; Vaccines - metabolism; Vaccins; United States; Virus; Design; Immunogenicity; HIV-1 virus; Retroviridae; Vaccine; Human immunodeficiency virus; Lentivirus
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/nbt.2197

Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do produce them after years of chronic HIV-1 infection have one or more unusual characteristics, including polyreactivity for host antigens, extensive somatic hypermutation and long, variable heavy-chain third complementarity-determining regions, factors that may limit their expression by host immunoregulatory mechanisms. The isolation of BnAbs from HIV-1–infected subjects and the use of computationally derived clonal lineages as templates provide a new path for HIV-1 vaccine immunogen design. This approach, which should be applicable to many infectious agents, holds promise for the construction of vaccines that can drive B cells along rare but desirable maturation pathways.