tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2015 Feb 17. pii: AAC.00118-15. [Epub ahead of print]
[h=1]Heterosubtyic Protection Conferred by the Human Monoclonal Antibody PN-SIA28 Against Influenza A Lethal Infections in Mice.[/h] Retamal M[SUP]1[/SUP], Abed Y[SUP]1[/SUP], Rh?aume C[SUP]1[/SUP], Cappelletti F[SUP]2[/SUP], Clementi N[SUP]2[/SUP], Mancini N[SUP]2[/SUP], Clementi M[SUP]2[/SUP], Burioni R[SUP]2[/SUP], Boivin G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] PN-SIA28 is a human monoclonal antibody (Hu-mAb) targeting highly conserved epitopes within the stem portion of the influenza hemagglutinin (Clementi et al., PLoS One, 2011). Previous in vitro studies demonstrated PN-SIA28 neutralizing activity against phylogenetically divergent influenza A subtypes. In this study, protective activity of PN-SIA28 was evaluated in mice inoculated with lethal influenza A/WSN/33 (H1N1), A/Quebec/144147/09 (H1N1pdm09) and A/Victoria/3/75 (H3N2) viruses. At 24 hours post-inoculation (p.i.), animals received intraperitoneally PN-SIA28 (1 or 10 mg/kg) or 10 mg/kg of unrelated Hu-mAb (mock). Body weight loss and mortality rate (MR) were recorded for 14 days p.i. Lung viral titers (LVT) were determined at day 5 p.i. In A/WSN/33 (H1N1)-infected groups, all untreated and mock-receiving mice died, whereas MRs of 87.5% and 25% were observed in mice that received PN-SIA28 at 1 and 10 mg/kg respectively. In A(H1N1)pdm09-infected groups, a MR of 75% was recorded in untreated and mock-treated groups, whereas 1 and 10 mg/kg PN-SIA28 groups had rates of 62.5% and 0% respectively. In A/Victoria/3/75 (H3N2)-infected animals, untreated and mock-treated animals had MRs of 37.5% and 25%, respectively, with no mortality recorded after PN-SIA28 treatments. Accordingly, PN-SIA28 treatments significantly reduced weight losses and resulted in ≥ 1-Log reduction in LVT when compared to control in all infection groups. This study confirms that antibodies targeting highly conserved epitopes in the influenza HA stem region, like PN-SIA28, not only neutralize influenza A viruses of clinically relevant subtypes in vitro but most importantly, protect from lethal influenza virus challenge in vivo.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25691648 [PubMed - as supplied by publisher]
[h=1]Heterosubtyic Protection Conferred by the Human Monoclonal Antibody PN-SIA28 Against Influenza A Lethal Infections in Mice.[/h] Retamal M[SUP]1[/SUP], Abed Y[SUP]1[/SUP], Rh?aume C[SUP]1[/SUP], Cappelletti F[SUP]2[/SUP], Clementi N[SUP]2[/SUP], Mancini N[SUP]2[/SUP], Clementi M[SUP]2[/SUP], Burioni R[SUP]2[/SUP], Boivin G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] PN-SIA28 is a human monoclonal antibody (Hu-mAb) targeting highly conserved epitopes within the stem portion of the influenza hemagglutinin (Clementi et al., PLoS One, 2011). Previous in vitro studies demonstrated PN-SIA28 neutralizing activity against phylogenetically divergent influenza A subtypes. In this study, protective activity of PN-SIA28 was evaluated in mice inoculated with lethal influenza A/WSN/33 (H1N1), A/Quebec/144147/09 (H1N1pdm09) and A/Victoria/3/75 (H3N2) viruses. At 24 hours post-inoculation (p.i.), animals received intraperitoneally PN-SIA28 (1 or 10 mg/kg) or 10 mg/kg of unrelated Hu-mAb (mock). Body weight loss and mortality rate (MR) were recorded for 14 days p.i. Lung viral titers (LVT) were determined at day 5 p.i. In A/WSN/33 (H1N1)-infected groups, all untreated and mock-receiving mice died, whereas MRs of 87.5% and 25% were observed in mice that received PN-SIA28 at 1 and 10 mg/kg respectively. In A(H1N1)pdm09-infected groups, a MR of 75% was recorded in untreated and mock-treated groups, whereas 1 and 10 mg/kg PN-SIA28 groups had rates of 62.5% and 0% respectively. In A/Victoria/3/75 (H3N2)-infected animals, untreated and mock-treated animals had MRs of 37.5% and 25%, respectively, with no mortality recorded after PN-SIA28 treatments. Accordingly, PN-SIA28 treatments significantly reduced weight losses and resulted in ≥ 1-Log reduction in LVT when compared to control in all infection groups. This study confirms that antibodies targeting highly conserved epitopes in the influenza HA stem region, like PN-SIA28, not only neutralize influenza A viruses of clinically relevant subtypes in vitro but most importantly, protect from lethal influenza virus challenge in vivo.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25691648 [PubMed - as supplied by publisher]