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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  

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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
Citation

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. "Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization." Cell 178.3 (2019) 567-584.e19