title: Heterosubtypic protection conferred by the human monoclonal antibody PN-SIA28 against influenza A virus lethal infections in mice.
abstract: PN-SIA28 is a human monoclonal antibody (Hu-MAb) targeting highly conserved epitopes within the stem portion of the influenza virus hemagglutinin (HA) (N. Clementi, et al, PLoS One 6:e28001, 2011, http://dx.doi.org/10.1371/journal.pone.0028001). Previous in vitro studies demonstrated PN-SIA28 neutralizing activities against phylogenetically divergent influenza A subtypes. In this study, the protective activity of PN-SIA28 was evaluated in mice inoculated with lethal influenza A/WSN/33 (H1N1), A/Quebec/144147/09 (H1N1)pdm09, and A/Victoria/3/75 (H3N2) viruses. At 24 h postinoculation (p.i.), animals received PN-SIA28 intraperitoneally (1 or 10 mg/kg of body weight) or 10 mg/kg of unrelated Hu-MAb (mock). Body weight loss and mortality rate (MR) were recorded for 14 days postinfection (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 1 and 10 mg/kg, respectively. In influenza A(H1N1) pdm09-infected groups, an MR of 75% was recorded for untreated and mock-treated groups, whereas the PN-SIA28 1-mg/kg and 10-mg/kg 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, and no mortalities were recorded after PN-SIA28 treatments. Accordingly, PN-SIA28 treatments significantly reduced weight losses and resulted in a ≥ 1-log reduction in LVT compared to the 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 also, more importantly, protect from a lethal influenza virus challenge in vivo.
authors.affiliation: Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Quebec, Canada.
authors.forename: Miguel
authors.initials: M
authors.lastname: Retamal
authors.affiliation: Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Quebec, Canada.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Abed
authors.affiliation: Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Quebec, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Rhéaume
authors.affiliation: Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cappelletti
authors.affiliation: Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Clementi
authors.affiliation: Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Mancini
authors.affiliation: Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
authors.affiliation: Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Quebec, Canada guy.boivin@crchul.ulaval.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity*; D007251:Influenza, Human / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents