| Literature DB >> 26091035 |
Pia Dosenovic1, Lotta von Boehmer1, Amelia Escolano1, Joseph Jardine2, Natalia T Freund1, Alexander D Gitlin1, Andrew T McGuire3, Daniel W Kulp2, Thiago Oliveira1, Louise Scharf4, John Pietzsch1, Matthew D Gray3, Albert Cupo5, Marit J van Gils6, Kai-Hui Yao1, Cassie Liu1, Anna Gazumyan7, Michael S Seaman8, Pamela J Björkman9, Rogier W Sanders10, John P Moore5, Leonidas Stamatatos11, William R Schief12, Michel C Nussenzweig13.
Abstract
A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.Entities:
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Year: 2015 PMID： 26091035 PMCID： PMC4604566 DOI： 10.1016/j.cell.2015.06.003
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582