PMID- 24739285 OWN - NLM STAT- MEDLINE DCOM- 20140912 LR - 20211021 IS - 1743-422X (Electronic) IS - 1743-422X (Linking) VI - 11 DP - 2014 Apr 16 TI - Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1 hemagglutinin and neuraminidase antibodies provides dose-dependent protection against lethal virus challenge in SCID mice. PG - 70 LID - 10.1186/1743-422X-11-70 [doi] AB - BACKGROUND: Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic. FINDINGS: 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). CONCLUSION: 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. FAU - Hohenadl, Christine AU - Hohenadl C FAU - Wodal, Walter AU - Wodal W FAU - Kerschbaum, Astrid AU - Kerschbaum A FAU - Fritz, Richard AU - Fritz R FAU - Howard, M Keith AU - Howard MK FAU - Farcet, Maria R AU - Farcet MR FAU - Portsmouth, Daniel AU - Portsmouth D FAU - McVey, John K AU - McVey JK FAU - Baker, Donald A AU - Baker DA FAU - Ehrlich, Hartmut J AU - Ehrlich HJ FAU - Barrett, P Noel AU - Barrett PN FAU - Kreil, Thomas R AU - Kreil TR AD - Global Pathogen Safety, Baxter BioScience, Benatzkygasse 2-6, 1221 Vienna, Austria. thomas_kreil@baxter.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140416 PL - England TA - Virol J JT - Virology journal JID - 101231645 RN - 0 (Antibodies, Viral) RN - 0 (Hemagglutinin Glycoproteins, Influenza Virus) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Viral Proteins) RN - EC 3.2.1.18 (NA protein, influenza A virus) RN - EC 3.2.1.18 (Neuraminidase) SB - IM MH - Animals MH - Antibodies, Viral/*administration & dosage MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Hemagglutinin Glycoproteins, Influenza Virus/*immunology MH - Immunocompromised Host MH - Immunoglobulins, Intravenous/*administration & dosage MH - Influenza A Virus, H1N1 Subtype/*immunology MH - Mice MH - Mice, SCID MH - Neuraminidase/*antagonists & inhibitors/immunology MH - Orthomyxoviridae Infections/*prevention & control MH - Survival Analysis MH - Treatment Outcome MH - Viral Proteins/*antagonists & inhibitors/immunology PMC - PMC3996311 EDAT- 2014/04/18 06:00 MHDA- 2014/09/13 06:00 PMCR- 2014/04/16 CRDT- 2014/04/18 06:00 PHST- 2014/01/24 00:00 [received] PHST- 2014/04/07 00:00 [accepted] PHST- 2014/04/18 06:00 [entrez] PHST- 2014/04/18 06:00 [pubmed] PHST- 2014/09/13 06:00 [medline] PHST- 2014/04/16 00:00 [pmc-release] AID - 1743-422X-11-70 [pii] AID - 10.1186/1743-422X-11-70 [doi] PST - epublish SO - Virol J. 2014 Apr 16;11:70. doi: 10.1186/1743-422X-11-70.