tetano
Editor, Senior Moderator
Biomed Environ Sci. 2020 Feb 20;33(2):103-113. doi: 10.3967/bes2020.014. [h=1]Cross-neutralizing Anti-hemagglutinin Antibodies Isolated from Patients Infected with Avian Influenza A (H5N1) Virus.[/h]
Sun Y[SUP]1[/SUP], Cao Y[SUP]2[/SUP], Li Z[SUP]1[/SUP], Bai T[SUP]1[/SUP], Zhang H[SUP]3[/SUP], Hu SX[SUP]3[/SUP], Li FC[SUP]3[/SUP], Zhao X[SUP]1[/SUP], Chen YK[SUP]4[/SUP], Lu J[SUP]1[/SUP], Liu LQ[SUP]1[/SUP], Wang DY[SUP]1[/SUP], Shu YL[SUP]4[/SUP], Zhou JF[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Objective:[/h] To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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 [SUB]H[/SUB]1-69-D2-15-J [SUB]H[/SUB]4 (2-12D5) and V [SUB]H[/SUB]1-2-D3-9-J [SUB]H[/SUB]5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA [SUB]2[/SUB] I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V [SUB]H[/SUB]1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively.
[h=4]Conclusions:[/h] 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.
[h=4]KEYWORDS:[/h] Antibody; Avian influenza A (H5N1) virus; Cross-neutralizing; D3-9; VH1-69
PMID: 32131957 DOI: 10.3967/bes2020.014
Sun Y[SUP]1[/SUP], Cao Y[SUP]2[/SUP], Li Z[SUP]1[/SUP], Bai T[SUP]1[/SUP], Zhang H[SUP]3[/SUP], Hu SX[SUP]3[/SUP], Li FC[SUP]3[/SUP], Zhao X[SUP]1[/SUP], Chen YK[SUP]4[/SUP], Lu J[SUP]1[/SUP], Liu LQ[SUP]1[/SUP], Wang DY[SUP]1[/SUP], Shu YL[SUP]4[/SUP], Zhou JF[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Objective:[/h] To recover broad-neutralizing monoclonal antibodies (BnAbs) from avian influenza A (H5N1) virus infection cases and investigate their genetic and functional features.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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 [SUB]H[/SUB]1-69-D2-15-J [SUB]H[/SUB]4 (2-12D5) and V [SUB]H[/SUB]1-2-D3-9-J [SUB]H[/SUB]5 (3-32G7.1), the BnAbs were directed toward CR6261-like epitopes in the HA stem, and HA [SUB]2[/SUB] I45 in the hydrophobic pocket was the critical residue for their binding. Signature motifs for binding with the HA stem, namely, IFY in V [SUB]H[/SUB]1-69-encoded Abs and LXYFXW in D3-9-encoded Abs, were also observed in 2-12D5 and 3-32G7.1, respectively.
[h=4]Conclusions:[/h] 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.
[h=4]KEYWORDS:[/h] Antibody; Avian influenza A (H5N1) virus; Cross-neutralizing; D3-9; VH1-69
PMID: 32131957 DOI: 10.3967/bes2020.014