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Nat Biotechnol. 2012 May 7;30(5):423-33. doi: 10.1038/nbt.2197.

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

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  • 1Duke Human Vaccine Institute, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.


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.

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