| Literature DB >> 25065977 |
Feng Gao1, Mattia Bonsignori2, Hua-Xin Liao2, Amit Kumar2, Shi-Mao Xia2, Xiaozhi Lu2, Fangping Cai2, Kwan-Ki Hwang2, Hongshuo Song2, Tongqing Zhou3, Rebecca M Lynch3, S Munir Alam2, M Anthony Moody2, Guido Ferrari2, Mark Berrong2, Garnett Kelsoe2, George M Shaw4, Beatrice H Hahn4, David C Montefiori2, Gift Kamanga5, Myron S Cohen6, Peter Hraber7, Peter D Kwong3, Bette T Korber7, John R Mascola3, Thomas B Kepler8, Barton F Haynes9.
Abstract
Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.Entities:
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Year: 2014 PMID： 25065977 PMCID： PMC4150607 DOI： 10.1016/j.cell.2014.06.022
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582