Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 541.3 Miscellaneous topics in physical chemistry
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2019
• Mô tả vật lý: Size: p. 567-584 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 259987
• Chủ đề: 1. 60 applied life sciences; 2. B cell ontogeny; 3. Broadly neutralizing antibody; 4. Fusion peptide; 5. Hiv-1 vaccine; 6. Immune monitoring; 7. Interaction hotspot; 8. Multidonor antibody class

Tóm tắt

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.