Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies

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Science  12 Dec 2014:
Vol. 346, Issue 6215, pp. 1380-1383
DOI: 10.1126/science.1259206

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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.

A fierce competition to attack HIV

The Holy Grail in the HIV field is a protective vaccine. However, because HIV mutates rapidly, it can escape from vaccine-elicited antibodies. Nevertheless, some HIV-positive individuals harbor antibodies that HIV cannot escape from very easily, so-called broadly neutralizing antibodies (bNAbs). McGuire et al. asked why these bNAbs don't win out over their more narrow brethren (nNAbs) early after infection (see the Perspective by Ofek and Diskin). They compared the responses of B cells carrying germline versions of nNAbs and bNAbs—that is, versions of these Abs that HIV would initially encounter—to HIV's envelope glycoprotein (Env). The nNAbs could recognize Env from a more diverse array of viruses compared to bNAbs, which puts them at a competitive advantage.

Science, this issue p. 1380; see also p. 1290

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