Serveur d'exploration sur les pandémies grippales

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A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic

Identifieur interne : 004478 ( Main/Exploration ); précédent : 004477; suivant : 004479

A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic

Auteurs : Yuk-Fai Lau [Singapour] ; Lay-Hoon Tang [Singapour] ; Eng-Eong Ooi [Singapour]

Source :

RBID : Pascal:09-0167946

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English descriptors

Abstract

The appearance and spread of the H5N1 highly pathogenic avian influenza (HPAI) raise concern of a possible pandemic. Current preventive measures include the development of a pre-pandemic influenza vaccine and stockpiling ofneuraminidase inhibitors. However, their benefits can be significantly reduced by mutations in the hemagglutinin or neuraminidase resulting in antigenic changes and the appearance of drug-resistance, respectively. Drugs that target the innate immune system to achieve a 'heightened antiviral' state represent another class of antiviral agents that could contribute to the control and treatment of influenza infection. In this study, PIKA (a stabilized dsRNA) provides broad-spectrum prophylaxis against a number of influenza A viruses. In addition, when PIKA was admixed with influenza vaccine preparations, including a formalin-inactivated whole-virion H5 vaccine, significant adjuvanting effect leading to accelerated viral clearance was observed in a murine model. These biological effects appear to be mediated by the ability of PIKA to promote the maturation of dendritic cells, including up-regulation of co-stimulatory molecules, such as CD80 and CD86, and the induction of various cytokines and chemokines. Toll-like receptor 3 (TLR3) was shown to recognize PIKA in a concentration-dependent manner. The potency and versatility in its activities make PIKA an attractive candidate for use in an influenza pandemic.

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<div type="abstract" xml:lang="en">The appearance and spread of the H5N1 highly pathogenic avian influenza (HPAI) raise concern of a possible pandemic. Current preventive measures include the development of a pre-pandemic influenza vaccine and stockpiling ofneuraminidase inhibitors. However, their benefits can be significantly reduced by mutations in the hemagglutinin or neuraminidase resulting in antigenic changes and the appearance of drug-resistance, respectively. Drugs that target the innate immune system to achieve a 'heightened antiviral' state represent another class of antiviral agents that could contribute to the control and treatment of influenza infection. In this study, PIKA (a stabilized dsRNA) provides broad-spectrum prophylaxis against a number of influenza A viruses. In addition, when PIKA was admixed with influenza vaccine preparations, including a formalin-inactivated whole-virion H5 vaccine, significant adjuvanting effect leading to accelerated viral clearance was observed in a murine model. These biological effects appear to be mediated by the ability of PIKA to promote the maturation of dendritic cells, including up-regulation of co-stimulatory molecules, such as CD80 and CD86, and the induction of various cytokines and chemokines. Toll-like receptor 3 (TLR3) was shown to recognize PIKA in a concentration-dependent manner. The potency and versatility in its activities make PIKA an attractive candidate for use in an influenza pandemic.</div>
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