Cell:實現人類異源HIV-1中和抗體B細胞譜系的疫苗誘導

2024年5月17日,美國杜克大學Barton F. Haynes等研究人員合作在在《細胞》雜志上發表了標題為“Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.”的研究成果,實現人類異源HIV-1中和抗體B細胞譜系疫苗誘導。

 

研究人員表示,HIV疫苗開發的一個關鍵障礙是無法在人類體內誘導出B細胞譜系的廣泛中和抗體(bnAb)。在HIV-1感染者中,bnAb需要數年才能形成。HVTN 133臨床試驗研究了一種針對B細胞譜系的HIV-1包膜(Env)膜近端外部區域(MPER)bnAb的肽/脂質體免疫原(NCT03934541)。

HIV-1中和抗體B細胞譜系

 

研究人員報告了MPER多肽脂質體誘導成熟bnAb及其前體的多克隆HIV-1 B細胞譜系,其中最有效的bnAb能中和15%的全球2級HIV-1毒株和35%的B族毒株,并在第二次免疫后啟動了B細胞譜系。疫苗選擇了不可能發生的突變,增加了抗體與gp41和脂質的結合,從而增強了中和效果。這項研究證明了,快速疫苗誘導具有異源中和活性的人類B細胞譜系和選擇抗體不可能突變的概念,并為成功開發HIV-1疫苗勾勒出了一條道路。

 

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.

 

文章來源:

Wilton B. Williams, S. Munir Alam, Gilad Ofek et al,Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.DOI: 10.1016/j.cell.2024.04.033,Cell:最新IF:66.85

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