tetano
Editor, Senior Moderator
F1000Res. 2017 Nov 15;6:2015. doi: 10.12688/f1000research.12999.1. eCollection 2017.
[h=1]IL-15 enhances cross-reactive antibody recall responses to seasonal H3 influenza viruses in vitro.[/h] Huang J[SUP]1[/SUP], Hilchey SP[SUP]2[/SUP], Wang J[SUP]2[/SUP], Gerigan J[SUP]2[/SUP], Zand MS[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Background: Recently, several human monoclonal antibodies that target conserved epitopes on the stalk region of influenza hemagglutinin (HA) have shown broad reactivity to influenza A subtypes. Also, vaccination with recombinant chimeric HA or stem fragments from H3 influenza viruses induce broad immune protection in mice and humans. However, it is unclear whether stalk-binding antibodies can be induced in human memory B cells by seasonal H3N2 viruses. Methods: In this study, we recruited 13 donors previously exposed to H3 viruses, the majority (12 of 13) of which had been immunized with seasonal influenza vaccines. We evaluated plasma baseline strain-specific and stalk-reactive anti-HA antibodies and B cell recall responses to inactivated H3N2 A/Victoria/361/2011 virus in vitro using a high throughput multiplex (mPlex-Flu) assay. Results: Stalk-reactive IgG was detected in the plasma of 7 of the subjects. Inactivated H3 viral particles rapidly induced clade cross-reactive antibodies in B cell cultures derived from all 13 donors. In addition, H3 stalk-reactive antibodies were detected in culture supernatants from 7 of the 13 donors (53.8%). H3 stalk-reactive antibodies were also induced by H1 and H7 subtypes. Interestingly, broadly cross-reactive antibody recall responses to H3 strains were also enhanced by stimulating B cells in vitro with CpG [SUB]2006[/SUB] ODN in the presence of IL-15. H3 stalk-reactive antibodies were detected in CpG [SUB]2006[/SUB] ODN + IL-15 stimulated B cell cultures derived from 12 of the 13 donors (92.3%), with high levels detected in cultures from 7 of the 13 donors. Conclusions: Our results demonstrate that stalk-reactive antibody recall responses induced by seasonal H3 viruses and CpG [SUB]2006[/SUB] ODN can be enhanced by IL-15.
[h=4]KEYWORDS:[/h] B Cell; CpG ODN; IL-15; Influenza immunity; hemagglutinin stalk
PMID: 29479423 PMCID: PMC5801566 DOI: 10.12688/f1000research.12999.1
[h=1]IL-15 enhances cross-reactive antibody recall responses to seasonal H3 influenza viruses in vitro.[/h] Huang J[SUP]1[/SUP], Hilchey SP[SUP]2[/SUP], Wang J[SUP]2[/SUP], Gerigan J[SUP]2[/SUP], Zand MS[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Background: Recently, several human monoclonal antibodies that target conserved epitopes on the stalk region of influenza hemagglutinin (HA) have shown broad reactivity to influenza A subtypes. Also, vaccination with recombinant chimeric HA or stem fragments from H3 influenza viruses induce broad immune protection in mice and humans. However, it is unclear whether stalk-binding antibodies can be induced in human memory B cells by seasonal H3N2 viruses. Methods: In this study, we recruited 13 donors previously exposed to H3 viruses, the majority (12 of 13) of which had been immunized with seasonal influenza vaccines. We evaluated plasma baseline strain-specific and stalk-reactive anti-HA antibodies and B cell recall responses to inactivated H3N2 A/Victoria/361/2011 virus in vitro using a high throughput multiplex (mPlex-Flu) assay. Results: Stalk-reactive IgG was detected in the plasma of 7 of the subjects. Inactivated H3 viral particles rapidly induced clade cross-reactive antibodies in B cell cultures derived from all 13 donors. In addition, H3 stalk-reactive antibodies were detected in culture supernatants from 7 of the 13 donors (53.8%). H3 stalk-reactive antibodies were also induced by H1 and H7 subtypes. Interestingly, broadly cross-reactive antibody recall responses to H3 strains were also enhanced by stimulating B cells in vitro with CpG [SUB]2006[/SUB] ODN in the presence of IL-15. H3 stalk-reactive antibodies were detected in CpG [SUB]2006[/SUB] ODN + IL-15 stimulated B cell cultures derived from 12 of the 13 donors (92.3%), with high levels detected in cultures from 7 of the 13 donors. Conclusions: Our results demonstrate that stalk-reactive antibody recall responses induced by seasonal H3 viruses and CpG [SUB]2006[/SUB] ODN can be enhanced by IL-15.
[h=4]KEYWORDS:[/h] B Cell; CpG ODN; IL-15; Influenza immunity; hemagglutinin stalk
PMID: 29479423 PMCID: PMC5801566 DOI: 10.12688/f1000research.12999.1