tetano
Editor, Senior Moderator
ell Host Microbe
. 2024 Dec 18:S1931-3128(24)00467-0.
doi: 10.1016/j.chom.2024.12.004. Online ahead of print. Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells
Xin Wang[SUP] 1 [/SUP], Huihui Kong[SUP] 2 [/SUP], Bingxin Chu[SUP] 3 [/SUP], Qian Yang[SUP] 1 [/SUP], Chaohui Lin[SUP] 1 [/SUP], Rui Liu[SUP] 4 [/SUP], Changxu Chen[SUP] 4 [/SUP], Yang Gao[SUP] 5 [/SUP], Guojun Wang[SUP] 5 [/SUP], Dayan Wang[SUP] 6 [/SUP], Chen Qin[SUP] 2 [/SUP], Xiaohua Ye[SUP] 1 [/SUP], Lifei Yu[SUP] 7 [/SUP], Xiangfei Xu[SUP] 7 [/SUP], Jie Jin[SUP] 7 [/SUP], Ren Sun[SUP] 8 [/SUP], Hualan Chen[SUP] 9 [/SUP], Xudong Wu[SUP] 10 [/SUP], Zeli Zhang[SUP] 11 [/SUP]
Affiliations
Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzymatic pocket and a separate epitope in the neighboring NA monomer. Furthermore, the NA BImAbs protect mice from the lethal challenge of the human pandemic H1N1 and H5N1. Our work demonstrates that the NA broad-inhibition precursor MBCs exist in healthy adults and could be targeted by the NA-based universal flu vaccine.
Keywords: broad-inhibition antibody; influenza virus; memory B cells; neuraminidase; pre-existing immunity.
. 2024 Dec 18:S1931-3128(24)00467-0.
doi: 10.1016/j.chom.2024.12.004. Online ahead of print. Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells
Xin Wang[SUP] 1 [/SUP], Huihui Kong[SUP] 2 [/SUP], Bingxin Chu[SUP] 3 [/SUP], Qian Yang[SUP] 1 [/SUP], Chaohui Lin[SUP] 1 [/SUP], Rui Liu[SUP] 4 [/SUP], Changxu Chen[SUP] 4 [/SUP], Yang Gao[SUP] 5 [/SUP], Guojun Wang[SUP] 5 [/SUP], Dayan Wang[SUP] 6 [/SUP], Chen Qin[SUP] 2 [/SUP], Xiaohua Ye[SUP] 1 [/SUP], Lifei Yu[SUP] 7 [/SUP], Xiangfei Xu[SUP] 7 [/SUP], Jie Jin[SUP] 7 [/SUP], Ren Sun[SUP] 8 [/SUP], Hualan Chen[SUP] 9 [/SUP], Xudong Wu[SUP] 10 [/SUP], Zeli Zhang[SUP] 11 [/SUP]
Affiliations
- PMID: 39740671
- DOI: 10.1016/j.chom.2024.12.004
Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzymatic pocket and a separate epitope in the neighboring NA monomer. Furthermore, the NA BImAbs protect mice from the lethal challenge of the human pandemic H1N1 and H5N1. Our work demonstrates that the NA broad-inhibition precursor MBCs exist in healthy adults and could be targeted by the NA-based universal flu vaccine.
Keywords: broad-inhibition antibody; influenza virus; memory B cells; neuraminidase; pre-existing immunity.