The development of a successful HIV-1 vaccine has been stymied by the inability to induce broadly neutralizing antibodies (bnAbs) to conserved regions of the HIV-1 envelope glycoprotein (Env) ( Burton et al., 2012 Mascola and Haynes, 2013), that include the CD4 binding site (CD4bs), the membrane external proximal region, and glycans and amino acid residues in the regions of the first (V1), second (V2) and third (V3) loops ( Burton et al., 2012 Kwong and Mascola, 2012 Sattentau and McMichael, 2010 Stamatatos, 2012 Walker et al., 2011 Walker et al., 2009 Zhou et al., 2010). Design of vaccine immunogens that simultaneously drive both autologous 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. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. We isolated an autologous 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. Here we study the B cell response in a bnAb-producing individual, and report cooperation between two B cell lineages to drive bnAb development. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority.
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