Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies

作者：McGuire Andrew T; Dreyer Anita M; Carbonetti Sara; Lippy Adriana; Glenn Jolene; Scheid Johannes F; Mouquet Hugo; Stamatatos Leonidas^*

来源：Science, 2014, 346(6215): 1380-1383.

DOI：10.1126/science.1259206

Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.

• 出版日期2014-12-12