西亚试剂：Cooperation of B Cell Lineages in Induction of HIV-1-Broadl

Feng Gao, Mattia Bonsignori, Hua-Xin Liao, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Fangping Cai, Kwan-Ki Hwang, Hongshuo Song,Tongqing Zhou, Rebecca M. Lynch, S. Munir Alam, M. Anthony Moody, Guido Ferrari, Mark Berrong, Garnett Kelsoe, George M. Shaw,Beatrice H. Hahn, David C. Montefiori, Gift Kamanga, Myron S. Cohen, Peter Hraber, Peter D. Kwong, Bette T. Korber, John R. Mascola,Thomas B. Kepler, Barton F. Haynes

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.

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