tetano
Editor, Senior Moderator
Science. 2018 Nov 2;362(6414):598-602. doi: 10.1126/science.aaq0620.
[h=1]Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.[/h] Laursen NS[SUP]1[/SUP], Friesen RHE[SUP]2[/SUP], Zhu X[SUP]1[/SUP], Jongeneelen M[SUP]3[/SUP], Blokland S[SUP]3[/SUP], Vermond J[SUP]4[/SUP], van Eijgen A[SUP]4[/SUP], Tang C[SUP]3[/SUP], van Diepen H[SUP]4[/SUP], Obmolova G[SUP]2[/SUP], van der Neut Kolfschoten M[SUP]3[/SUP], Zuijdgeest D[SUP]3[/SUP], Straetemans R[SUP]5[/SUP], Hoffman RMB[SUP]1[/SUP], Nieusma T[SUP]1[/SUP], Pallesen J[SUP]1[/SUP], Turner HL[SUP]1[/SUP], Bernard SM[SUP]1[/SUP], Ward AB[SUP]1[/SUP], Luo J[SUP]2[/SUP], Poon LLM[SUP]6[/SUP], Tretiakova AP[SUP]7[/SUP], Wilson JM[SUP]7[/SUP], Limberis MP[SUP]7[/SUP], Vogels R[SUP]3[/SUP], Brandenburg B[SUP]3[/SUP], Kolkman JA[SUP]8[/SUP], Wilson IA[SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.
PMID: 30385580 DOI: 10.1126/science.aaq0620
[h=1]Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.[/h] Laursen NS[SUP]1[/SUP], Friesen RHE[SUP]2[/SUP], Zhu X[SUP]1[/SUP], Jongeneelen M[SUP]3[/SUP], Blokland S[SUP]3[/SUP], Vermond J[SUP]4[/SUP], van Eijgen A[SUP]4[/SUP], Tang C[SUP]3[/SUP], van Diepen H[SUP]4[/SUP], Obmolova G[SUP]2[/SUP], van der Neut Kolfschoten M[SUP]3[/SUP], Zuijdgeest D[SUP]3[/SUP], Straetemans R[SUP]5[/SUP], Hoffman RMB[SUP]1[/SUP], Nieusma T[SUP]1[/SUP], Pallesen J[SUP]1[/SUP], Turner HL[SUP]1[/SUP], Bernard SM[SUP]1[/SUP], Ward AB[SUP]1[/SUP], Luo J[SUP]2[/SUP], Poon LLM[SUP]6[/SUP], Tretiakova AP[SUP]7[/SUP], Wilson JM[SUP]7[/SUP], Limberis MP[SUP]7[/SUP], Vogels R[SUP]3[/SUP], Brandenburg B[SUP]3[/SUP], Kolkman JA[SUP]8[/SUP], Wilson IA[SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.
PMID: 30385580 DOI: 10.1126/science.aaq0620