Abstract
BACKGROUND: Influenza, particularly novel zoonotic strains, causes severe disease in immunocompromised persons (ISPs). Global outbreaks of highly pathogenic avian influenza (HPAI, e.g., H5N1, H7N9) may pose similar risk to ISPs, yet anti-HPAI immune landscape and impact of vaccination are unknown. [Figure: see text] [Figure: see text] METHODS: In an ongoing national prospective cohort of ISPs reporting respiratory virus vaccination and infection, plasma from participants was analyzed for binding antibody (Ab) against seasonal (H1, H3) and HPAI (H7) hemagglutinin (HA) using a multiplex electrochemiluminescence assay (Meso Scale Discovery) and microneutralization using live contemporary vaccine strains of H1N1 and H3N2 before and after seasonal influenza vaccination. Changes in HA binding titer and neutralization were evaluated using Wilcoxon Signed Rank testing. Interstrain HA binding Pearson correlations were computed along with intrastrain HA binding and neutralization. [Figure: see text] [Figure: see text] RESULTS: Among 11 ISPs, median [IQR] anti H1, H3, H7 titers did not change significantly from baseline (4.9 [4.7 – 5.0], 4.4 [4.3 – 4.6], and 3.7 [3.5 – 4] arbitrary units (AU)/mL, respectively) to 4 weeks after vaccination (4.9 [4.8 – 5.3], 4.6 [ 4.4 – 4.8], and 3.9 [3.7 - 4], respectively; p >0.05 for all) (Fig1). H7 titers were ∼5-fold and ∼11-fold lower than vs H3 and H1, respectively. Median area under the curve (AUC) neutralization was similar between baseline and 4 weeks for H1N1 (1.5 [1.1 – 1.8] to 1.5 [1.1 – 2.4], p = 0.23) but significantly increased for H3N2 (0.03 [0 – 0.6] to 0.06 [0 – 0.5], p < 0.05) (Fig2). H3 binding was positively correlated with H1 (r = 0.75, p< 0.05) and H7 (r = 0.58, p< 0.05), but H1 and H7 titers did not correlate (r = 0.21, p >0.05) (Fig3). H1 binding and neutralization were positively correlated (r = 0.65, p< 0.05), but H3 binding and neutralization were not significantly correlated (r = 0.04, p >0.05). CONCLUSION: Anti-HPAI humoral immunity appears low in ISPs without substantial boosting by vaccination, raising concern for vulnerability to infection and disease. H3 binding may be associated with betters cross-reactivity with H7 than H1. Anti-H5 Ab evaluation is ongoing and of high importance given widespread H5N1 circulation and potential threat to ISPs. DISCLOSURES: William Werbel, MD PhD, AstraZeneca: Advisor/Consultant|Novavax: Advisor/Consultant Andrew H. Karaba, MD PhD, GSK: Advisor/Consultant|Hologic: Advisor/Consultant