tetano
Editor, Senior Moderator
J Virol. 2017 Jan 11. pii: JVI.02500-16. doi: 10.1128/JVI.02500-16. [Epub ahead of print]
[h=1]Hierarchical and redundant roles of activating FcγRs in protection against influenza disease by M2e-specific IgG1 and IgG2a antibodies.[/h] Van den Hoecke S[SUP]1,[/SUP][SUP]2[/SUP], Ehrhardt K[SUP]3[/SUP], Kolpe A[SUP]1,[/SUP][SUP]2[/SUP], El Bakkouri K[SUP]1,[/SUP][SUP]2[/SUP], Deng L[SUP]1,[/SUP][SUP]2[/SUP], Grootaert H[SUP]1,[/SUP][SUP]4[/SUP], Schoonooghe S[SUP]5,[/SUP][SUP]6[/SUP], Smet A[SUP]1,[/SUP][SUP]2[/SUP], Bentahir M[SUP]1,[/SUP][SUP]2[/SUP], Roose K[SUP]1,[/SUP][SUP]2[/SUP], Schotsaert M[SUP]1,[/SUP][SUP]2[/SUP], Schepens B[SUP]1,[/SUP][SUP]2[/SUP], Callewaert N[SUP]1,[/SUP][SUP]4[/SUP], Nimmerjahn F[SUP]7[/SUP], Staeheli P[SUP]3[/SUP], Hengel H[SUP]3[/SUP], Saelens X[SUP]8,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas mAb 37 only activated FcγRIII. Passive transfer of mAb 37 or mAb 65 in wild type, Fcer1g[SUP]-/-[/SUP], Fcgr3[SUP]-/-[/SUP] and Fcgr1[SUP]-/-[/SUP] Fcgr3[SUP]-/-[/SUP] BALB/c mice revealed the importance of these receptors for protection against influenza A virus challenge, with a clear requirement of FcγRIII for IgG1 mAb 37. We also report that FcγRIV contributes to protection by M2e-specific IgG2a antibodies.
[h=4]IMPORTANCE:[/h] There is increased awareness that protection by antibodies directed against viral antigens is also mediated by the Fc domain of these antibodies. These Fc-mediated effector functions are often missed in clinical assays, which are used for example to define correlates of protection induced by vaccines. The use of antibodies to prevent and treat infectious diseases is on the rise, and has proven a promising approach in our battle against newly emerging viral infections. It is now also realized that Fcγ receptors significantly enhance the in vivo protective effect of broadly neutralizing antibodies directed against the conserved parts of the influenza virus hemagglutinin. We show here that two M2e-specific monoclonal antibodies with close to identical antigen- binding specificity and affinity have a very different in vivo protective potential that is controlled by their capacity to interact with activating Fcγ receptors.
Copyright ? 2017 American Society for Microbiology.
PMID: 28077656 DOI: 10.1128/JVI.02500-16
[PubMed - as supplied by publisher]
[h=1]Hierarchical and redundant roles of activating FcγRs in protection against influenza disease by M2e-specific IgG1 and IgG2a antibodies.[/h] Van den Hoecke S[SUP]1,[/SUP][SUP]2[/SUP], Ehrhardt K[SUP]3[/SUP], Kolpe A[SUP]1,[/SUP][SUP]2[/SUP], El Bakkouri K[SUP]1,[/SUP][SUP]2[/SUP], Deng L[SUP]1,[/SUP][SUP]2[/SUP], Grootaert H[SUP]1,[/SUP][SUP]4[/SUP], Schoonooghe S[SUP]5,[/SUP][SUP]6[/SUP], Smet A[SUP]1,[/SUP][SUP]2[/SUP], Bentahir M[SUP]1,[/SUP][SUP]2[/SUP], Roose K[SUP]1,[/SUP][SUP]2[/SUP], Schotsaert M[SUP]1,[/SUP][SUP]2[/SUP], Schepens B[SUP]1,[/SUP][SUP]2[/SUP], Callewaert N[SUP]1,[/SUP][SUP]4[/SUP], Nimmerjahn F[SUP]7[/SUP], Staeheli P[SUP]3[/SUP], Hengel H[SUP]3[/SUP], Saelens X[SUP]8,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas mAb 37 only activated FcγRIII. Passive transfer of mAb 37 or mAb 65 in wild type, Fcer1g[SUP]-/-[/SUP], Fcgr3[SUP]-/-[/SUP] and Fcgr1[SUP]-/-[/SUP] Fcgr3[SUP]-/-[/SUP] BALB/c mice revealed the importance of these receptors for protection against influenza A virus challenge, with a clear requirement of FcγRIII for IgG1 mAb 37. We also report that FcγRIV contributes to protection by M2e-specific IgG2a antibodies.
[h=4]IMPORTANCE:[/h] There is increased awareness that protection by antibodies directed against viral antigens is also mediated by the Fc domain of these antibodies. These Fc-mediated effector functions are often missed in clinical assays, which are used for example to define correlates of protection induced by vaccines. The use of antibodies to prevent and treat infectious diseases is on the rise, and has proven a promising approach in our battle against newly emerging viral infections. It is now also realized that Fcγ receptors significantly enhance the in vivo protective effect of broadly neutralizing antibodies directed against the conserved parts of the influenza virus hemagglutinin. We show here that two M2e-specific monoclonal antibodies with close to identical antigen- binding specificity and affinity have a very different in vivo protective potential that is controlled by their capacity to interact with activating Fcγ receptors.
Copyright ? 2017 American Society for Microbiology.
PMID: 28077656 DOI: 10.1128/JVI.02500-16
[PubMed - as supplied by publisher]