Tweet
Biomed Environ Sci. 2020 Feb 20;33(2):103-113. doi: 10.3967/bes2020.014. Cross-neutralizing Anti-hemagglutinin Antibodies Isolated from Patients Infected with Avian Influenza A (H5N1) Virus.
Sun Y1, Cao Y2, Li Z1, Bai T1, Zhang H3, Hu SX3, Li FC3, Zhao X1, Chen YK4, Lu J1, Liu LQ1, Wang DY1, Shu YL4, Zhou JF1.
Author information
Abstract
Objective:
To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features.
Methods:
We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients. The genetic basis, biological functions, and epitopes of the obtained BnAbs were assessed and modeled.
Results:
Two BnAbs, 2-12D5, and 3-37G7.1, were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset. Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity (ADCC) activity. Albeit derived from distinct Ab lineages, i.e., V H1-69-D2-15-J H4 (2-12D5) and V H1-2-D3-9-J H5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA 2 I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V H1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively.
Conclusions:
Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus. The HA stem epitopes targeted by the BnAbs, and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
Copyright ? 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.
KEYWORDS:
Antibody; Avian influenza A (H5N1) virus; Cross-neutralizing; D3-9; VH1-69
PMID: 32131957 DOI: 10.3967/bes2020.014