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

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.

Characterization of source plasma from self‐identified vaccinated or convalescent donors during the 2009 H1N1 pandemic

“…To speed production, individual plasma donations were pooled based on self‐reported history and not tested for the presence of neutralizing influenza antibodies prior to FLUIGIV production. The resulting product had high anti‐pdmH1N1 antibody levels and protected immune‐deficient mice from lethal disease . Protection against lethal challenge with the mouse‐adapted pandemic strain A/California/04/09 in a preexposure prophylaxis study was also observed in immunocompetent BALB/c mice (A. M. Khalenkov and D. Scott, unpublished data, 2017).…”

Pigs with Severe Combined Immunodeficiency Are Impaired in Controlling Influenza A Virus Infection

“…Thus these pigs provide an additional model to study the immune response mechanisms involved in the protection and/or resolution of IAV infection, particularly in regards to the adaptive compartment of the immune system. Because swine are natural hosts for IAV, are genetically and anatomically similar to humans [36], and also have an immune genome component that is very similar to humans [37], these SCID pigs represent an improved model to the use of SCID mice to evaluate potential therapies and preventive strategies for human influenza [38]. …”

Prevalence of neutralizing antibodies to common respiratory viruses in intravenous immunoglobulin and in healthy donors in southern China

“…One potential therapeutic option is passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (H-IVIG) (12). Previous work has suggested that this approach might be an effective treatment for infections with Spanish InfA (H1N1), avian InfA (H5N1), 2009 pandemic InfA (H1N1), SARS coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), among others (12)(13)(14)(15)(16)(17)(18). However, few studies have been reported using this approach for the most prevalent viral pathogens.…”