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

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

Cell (2019-07-28)

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, Tongqing Zhou, Gwo-Yu Chuang, Cara W Chao, Ying Gu, Alexander J Jafari, Mark K Louder, Sijy O'Dell, Ariana P Rowshan, Elise G Viox, Yiran Wang, Chang W Choi, Martin M Corcoran, Angela R Corrigan, Venkata P Dandey, Edward T Eng, Hui Geng, Kathryn E Foulds, Yicheng Guo, Young D Kwon, Bob Lin, Kevin Liu, Rosemarie D Mason, Martha C Nason, Tiffany Y Ohr, Li Ou, Reda Rawi, Edward K Sarfo, Arne Schön, John P Todd, Shuishu Wang, Hui Wei, Winston Wu, James C Mullikin, Robert T Bailer, Nicole A Doria-Rose, Gunilla B Karlsson Hedestam, Diana G Scorpio, Julie Overbaugh, Jesse D Bloom, Bridget Carragher, Clinton S Potter, Lawrence Shapiro, Peter D Kwong, John R Mascola

PMID31348886

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-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.