title: B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study.
abstract: 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.
authors.affiliation: Duke Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. hayne002@mc.duke.edu
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001402:B-Lymphocytes / Q000166:cytology*; D001665:Binding Sites; D001709:Biotechnology / Q000379:methods; D019070:Cell Lineage; D049109:Cell Proliferation; D019281:Dimerization; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry; D015483:HIV Antibodies / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007125:Immunogenetics; D009154:Mutation; D009500:Neutralization Tests; D014612:Vaccines / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D014612:Vaccines