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Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization

Cell. 2019-07; 
Kong R, Duan H, Sheng Z, Xu K, Acharya P, Chen X, Cheng C, Dingens AS, Gorman J, Sastry M, Shen CH, Zhang B, Zhou T, Chuang GY, Chao CW, Gu Y, Jafari AJ, Louder MK, O'Dell S, Rowshan AP, Viox EG, Wang Y, Choi CW, Corcoran MM, Corrigan AR, Dandey VP, Eng ET, Geng H, Foulds KE, Guo Y, Kwon YD, Lin B, Liu K, Mason RD, Nason MC, Ohr TY, Ou L, Rawi R, Sarfo EK, Schön A, Todd JP, Wang S, Wei H, Wu W; NISC Comparative Sequencing Program0, Mullikin JC0, Bailer RT, Doria-Rose NA, Karlsson Hedestam GB, Scorpio DG, Overbaugh J, Bloom JD, Carragher B, Potter CS, Shapiro L, Kwong PD, Mascola JR
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Peptide Synthesis FP8 peptide: AVGIGAVFC,FP7 peptide: AVGIGAVC,FP6 peptide: AVGIGAC,FP9-PEG12-biotin(Genscript)...HIV-1 fusion peptide (FP8: AVGIGAVFC, FP7: AVGIGAVC, FP6: AVGIGAC) were synthesized (GenScript) with a free amine at the N terminus and an extra cysteine residue appended to the C terminus...Another FP probe, a soluble probe, was constructed by attaching a linear peptide comprising the N-terminal 9 residues of FP (FP9) through a polyethylene glycol linker to biotin (synthesized by Genscript) and conjugated to streptavidin-PE (Invitrogen, S21388). Get A Quote

摘要

The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-e... More

关键词

B cell ontogeny; HIV-1 vaccine; broadly neutralizing antibody; fusion peptide; immune monitoring; interaction hotspot; multidonor antibody class
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