Journal
CELL
Volume 166, Issue 1, Pages 77-87Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.05.055
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Funding
- NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH [12670]
- NIH [R01 AI076105, R01 AI103981, R01 AI120961, R21 AI112389, F30 AI122866, T32 AI083203]
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HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at similar to 1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.
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