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.
Highlights
Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic
We further characterized postpandemic H-Intravenous immunoglobulin (IVIG) preparations with respect to HI and MN antibodies against both pandemic H1N1 (pH1N1) and a seasonal H1N1 virus (A/New Caledonia/20/1999, which circulated in the Northern hemisphere and was a recommended component of the trivalent seasonal vaccine from 2000–01 to 2006–07)
To investigate the titers of antibodies against seasonal H1N1 (sH1N1) and pH1N1 in pre-pandemic (n = 13) and post-pandemic IVIG (n = 2) preparations, sera were analyzed by HI, MN and NAi assays
Summary
Convalescent plasma and fractionated immunoglobulins have been suggested as prophylactic or therapeutic interventions during an influenza pandemic. The use of convalescent plasma and fractionated immunoglobulins [3,4], and, more recently, monoclonal antibodies [5,6,7,8], has been suggested as a complementary strategy to prevent or treat virus infection during an influenza pandemic. We further characterized postpandemic H-IVIG preparations with respect to HI and MN antibodies against both pH1N1 and a seasonal H1N1 (sH1N1) virus (A/New Caledonia/20/1999, which circulated in the Northern hemisphere and was a recommended component of the trivalent seasonal vaccine from 2000–01 to 2006–07). We investigated the extent to which antibodies capable of inhibiting the enzymatic activity of the sH1N1 and pH1N1 neuraminidase (NA) antigens were enriched in the post-pandemic compared to pre-pandemic preparations. We investigated the ability of pre-pandemic IVIG and post-pandemic H-IVIG to protect highly susceptible immunodeficient SCID mice against challenge with wild-type pH1N1 virus
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