2025-03-04 アルゴンヌ国立研究所 (ANL)
<関連情報>
- https://www.anl.gov/article/new-hiv-vaccine-candidate-discovered-with-help-from-argonnes-advanced-photon-source
- https://www.cell.com/cell/fulltext/S0092-8674(24)00459-8
ヒトにおける異種HIV-1中和抗体B細胞系列のワクチン誘導 Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans
Wilton B. Williams, wilton.williams∙ S. Munir Alam∙ Gilad Ofek∙ … ∙ Stephen R. Walsh∙ Lindsey R. Baden lbaden∙ Barton F. Haynes
Cell Published:May 17, 2024
DOI:https://doi.org/10.1016/j.cell.2024.04.033
Graphical abstract
Highlights
•HIV gp41 MPER peptide-liposome vaccine elicited polyclonal NAbs in humans
•Vaccine-induced MPER-reactive antibodies matured from precursors to bnAb status
•Vaccine-selected improbable mutations conferred lipid binding and HIV neutralization
•MPER bnAb lineage was initiated after two immunizations
Summary
A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.
