5f6h
Crystal Structure of Tier 2 Neutralizing Antibody DH427 from a Rhesus Macaque
Structural highlights
Publication Abstract from PubMedAntibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.,Bradley T, Fera D, Bhiman J, Eslamizar L, Lu X, Anasti K, Zhang R, Sutherland LL, Scearce RM, Bowman CM, Stolarchuk C, Lloyd KE, Parks R, Eaton A, Foulger A, Nie X, Karim SS, Barnett S, Kelsoe G, Kepler TB, Alam SM, Montefiori DC, Moody MA, Liao HX, Morris L, Santra S, Harrison SC, Haynes BF Cell Rep. 2016 Jan 5;14(1):43-54. doi: 10.1016/j.celrep.2015.12.017. Epub 2015, Dec 24. PMID:26725118[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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