title: Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1 hemagglutinin and neuraminidase antibodies provides dose-dependent protection against lethal virus challenge in SCID mice.
abstract: BACKGROUND
  Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic.
  
  
  RESULTS
  Intravenous immunoglobulin (IVIG) preparations manufactured from human plasma collected before the 2009 H1N1 influenza pandemic, and post-pandemic hyperimmune (H)-IVIG preparations were characterized with respect to hemagglutination inhibition (HI), microneutralization (MN) and neuraminidase-inhibiting (NAi) antibody titers against pandemic H1N1 (pH1N1) and seasonal H1N1 (sH1N1) viruses. The protective efficacy of the IVIG and H-IVIG preparations was evaluated in a SCID mouse challenge model.Substantial levels of HI, MN and NAi antibodies against pH1N1 (GMTs 1:45, 1:204 and 1: 727, respectively) and sH1N1 (GMTs 1:688, 1:4,946 and 1:312, respectively) were present in pre-pandemic IVIG preparations. In post-pandemic H-IVIG preparations, HI, MN and NAi antibody GMTs against pH1N1 were 1:1,280, 1:11,404 and 1:2,488 (28-, 56- and 3.4-fold enriched), respectively, compared to pre-pandemic IVIG preparations (p < 0.001). Post-pandemic H-IVIG (HI titer 1:1,280) provided complete protection from lethality of SCID mice against pH1N1 challenge (100% of mice survived for 29 days post-challenge). Pre-pandemic IVIG (HI titer 1:70) did not provide significant protection against pH1N1 challenge (50% of mice survived 29 days post-challenge compared to 40% survival in the buffer control group). There was a highly significant correlation between circulating in vivo HI and MN antibody titers and survival (p < 0001).
  
  
  CONCLUSIONS
  The substantial enrichment of HA- and NA-specific antibodies in H-IVIG and the efficacious protection of SCID mice against challenge with pH1N1 suggests H-IVIG as a promising intervention against pandemic influenza for immunocompromised patients and other risk groups.
authors.forename: Christine
authors.initials: C
authors.lastname: Hohenadl
authors.forename: Walter
authors.initials: W
authors.lastname: Wodal
authors.forename: Astrid
authors.initials: A
authors.lastname: Kerschbaum
authors.forename: Richard
authors.initials: R
authors.lastname: Fritz
authors.forename: M Keith
authors.initials: MK
authors.lastname: Howard
authors.forename: Maria R
authors.initials: MR
authors.lastname: Farcet
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
authors.forename: John K
authors.initials: JK
authors.lastname: McVey
authors.forename: Donald A
authors.initials: DA
authors.lastname: Baker
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.affiliation: Global Pathogen Safety, Baxter BioScience, Benatzkygasse 2-6, 1221 Vienna, Austria. thomas_kreil@baxter.com.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D016019:Survival Analysis; D016896:Treatment Outcome; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016756:Immunoglobulins, Intravenous; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase
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