Journal
SCIENCE
Volume 346, Issue 6215, Pages 1380-1383Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1259206
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Funding
- NIH [P01 AI094419-01, U19 19AI109632-01]
- Canadian Institutes of Health Research
- Swiss National Science Foundation [PBBSP3_144245, P300P3_151140]
- Swiss National Science Foundation (SNF) [P300P3_151140, PBBSP3_144245] Funding Source: Swiss National Science Foundation (SNF)
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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.
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