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

Rui Kong, Hongying Duan, Zizhang Sheng, Kai Xu, Priyamvada Acharya, Xuejun Chen, Cheng Cheng, Adam S. Dingens, Jason Gorman, Mallika Sastry, Chen-Hsiang Shen, Baoshan Zhang (+44 others)
2019 Cell  
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
more » ... al 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-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
doi:10.1016/j.cell.2019.06.030 pmid:31348886 pmcid:PMC6755680 fatcat:as56226nyrhxtc7eziedwb7wzq