Preparation of commercial quantities of a hyperimmune human intravenous immunoglobulin preparation against an emerging infectious disease: the example of pandemic H1N1 influenza

Kreil, Thomas R.; Vey, John K. Mc; Lei, Laura Shau‐Ping; Camacho, Laureano; Wodal, Walter; Kerschbaum, Astrid; Segura, E Vélez; Vandamme, E.; Gavit, Patrick; Ehrlich, Hartmut J.; Barrett, Perry; Baker, D.

doi:10.1111/j.1537-2995.2011.03347.x

Cited by 19 publications

(24 citation statements)

References 30 publications

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“…Intravenous immunoglobulin91011 and influenza-specific monoclonal antibodies (mAbs), particularly those that bind to the conserved, stem region of the haemagglutinin (HA)121314, are also being considered as alternative treatments. mAbs that inhibit the enzyme activity of NA also have the potential to serve as therapeutic agents15161718.…”

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confidence: 99%

Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

et al. 2015

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A(H1N1)pdm09 influenza A viruses predominated in the 2013–2014 USA influenza season, and although most of these viruses remain sensitive to Food and Drug Administration-approved neuraminidase (NA) inhibitors, alternative therapies are needed. Here we show that monoclonal antibody CD6, selected for binding to the NA of the prototypic A(H1N1)pdm09 virus, A/California/07/2009, protects mice against lethal virus challenge. The crystal structure of NA in complex with CD6 Fab reveals a unique epitope, where the heavy-chain complementarity determining regions (HCDRs) 1 and 2 bind one NA monomer, the light-chain CDR2 binds the neighbouring monomer, whereas HCDR3 interacts with both monomers. This 30-amino-acid epitope spans the lateral face of an NA dimer and is conserved among circulating A(H1N1)pdm09 viruses. These results suggest that the large, lateral CD6 epitope may be an effective target of antibodies selected for development as therapeutic agents against circulating H1N1 influenza viruses.

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Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

et al. 2015

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“…As previously reported [11], we investigated the feasibility of manufacturing H-IVIG as a response to the emergence of the 2009 H1N1 pandemic (pH1N1) virus. H-IVIG preparations were shown to have significantly elevated levels of pH1N1 hemagglutinating (HI) and neutralizing antibodies, as assessed by microneutralization (MN) assay, compared to standard IVIG preparations collected from donors either during or before the H1N1 pandemic [11].…”

Section: Introductionmentioning

confidence: 99%

“…H-IVIG preparations were shown to have significantly elevated levels of pH1N1 hemagglutinating (HI) and neutralizing antibodies, as assessed by microneutralization (MN) assay, compared to standard IVIG preparations collected from donors either during or before the H1N1 pandemic [11]. …”

Section: Introductionmentioning

confidence: 99%

Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1 hemagglutinin and neuraminidase antibodies provides dose-dependent protection against lethal virus challenge in SCID mice

Hohenadl

Wodal

Kerschbaum

et al. 2014

Virol J

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BackgroundConvalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic.FindingsIntravenous 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).ConclusionThe 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.

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“…The feasibility of this approach has recently been confirmed at commercial scale during the 2009 influenza A(H1N1) pandemic ( 15 ). The US-based donor population for this preparation was, however, fully qualified and consistent with the stringent standards required for current plasma fractionation, a situation entirely different from the biosafety challenges associated with bringing reconvalescent plasma from the current Ebola-endemic regions into fractionation facilities licensed according to good manufacturing practices.…”

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Treatment of Ebola Virus Infection with Antibodies from Reconvalescent Donors

Kreil¹

2015

Emerg. Infect. Dis.

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Preparation of commercial quantities of a hyperimmune human intravenous immunoglobulin preparation against an emerging infectious disease: the example of pandemic H1N1 influenza

Abstract: This work demonstrates the feasibility of producing a H-IVIG preparation at large scale relatively rapidly, with a significant enrichment in antibodies to the H1N1 influenza, achieved by donor self-identification.

Cited by 19 publications

References 30 publications

Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers

Hyperimmune intravenous immunoglobulin containing high titers of pandemic H1N1 hemagglutinin and neuraminidase antibodies provides dose-dependent protection against lethal virus challenge in SCID mice

Treatment of Ebola Virus Infection with Antibodies from Reconvalescent Donors

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