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Enhanced Inhibition of Influenza A Virus Adhesion by Di- and Trivalent Hemagglutinin Inhibitors.

ABSTRACT: Multivalent carbohydrate-based ligands were synthesized and evaluated as inhibitors of the adhesion protein HA of the influenza A virus (IAV). HA relies on multivalency for strong viral adhesion. While viral adhesion inhibition by large polymeric molecules has proven viable, limited success was reached for smaller multivalent compounds. By linking of sialylated LAcNAc units to di- and trivalent scaffolds, inhibitors were obtained with an up to 428-fold enhanced inhibition in various assays.

SUBMITTER: Lu W

PROVIDER: S-EPMC6627469 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Enhanced Inhibition of Influenza A Virus Adhesion by Di- and Trivalent Hemagglutinin Inhibitors.

Lu Wenjing W Du Wenjuan W Somovilla Victor J VJ Yu Guangyun G Haksar Diksha D de Vries Erik E Boons Geert-Jan GJ de Vries Robert P RP de Haan Cornelis A M CAM Pieters Roland J RJ

Journal of medicinal chemistry 20190628 13

Multivalent carbohydrate-based ligands were synthesized and evaluated as inhibitors of the adhesion protein HA of the influenza A virus (IAV). HA relies on multivalency for strong viral adhesion. While viral adhesion inhibition by large polymeric molecules has proven viable, limited success was reached for smaller multivalent compounds. By linking of sialylated LAcNAc units to di- and trivalent scaffolds, inhibitors were obtained with an up to 428-fold enhanced inhibition in various assays. ...[more]

PMID: 31251606

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Project description:BackgroundThe conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness.MethodsOne hundred forty-five human immunodeficiency virus (HIV)-uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction.ResultsIncreases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers.ConclusionsH1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus.

Dataset Information

Enhanced Inhibition of Influenza A Virus Adhesion by Di- and Trivalent Hemagglutinin Inhibitors.

Publications

Enhanced Inhibition of Influenza A Virus Adhesion by Di- and Trivalent Hemagglutinin Inhibitors.

Similar Datasets

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