Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.
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.
Gao, F; Bonsignori, M; Liao, H-X; Kumar, A; Xia, S-M; Lu, X; Cai, F; Hwang, K-K; Song, H; Zhou, T; Lynch, RM; Alam, SM; Moody, MA; Ferrari, G; Berrong, M; Kelsoe, G; Shaw, GM; Hahn, BH; Montefiori, DC; Kamanga, G; Cohen, MS; Hraber, P; Kwong, PD; Korber, BT; Mascola, JR; Kepler, TB; Haynes, BF
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