Cooperation of B Cell Lineages in Induction of HIV-1-Broadly Neutralizing Antibodies

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:
  • Cell

دوره 158  شماره 

صفحات  -

تاریخ انتشار 2014