Dissemin is shutting down on January 1st, 2025

Published in

Nature Research, Nature Biotechnology, 5(30), p. 423-433, 2012

DOI: 10.1038/nbt.2197

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.