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 : 004086 ( Main/Merge ); précédent : 004085; suivant : 004087A 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 ; Lay-Hoon Tang ; Eng-Eong OoiSource :
- Vaccine [ 0264-410X ] ; 2009.
Descripteurs français
- KwdFr :
- ARN double brin (génétique), ARN viral (génétique), Administration par voie nasale, Animaux, Anticorps antiviraux (génétique), Anticorps antiviraux (immunologie), Flambées de maladies, Grippe chez les oiseaux (génétique), Grippe chez les oiseaux (immunologie), Grippe chez les oiseaux (virologie), Grippe humaine (immunologie), Grippe humaine (épidémiologie), Humains, Mâle, Oiseaux, Récepteur de type Toll-3 (génétique), Réplication virale, Souris, Souris de lignée BALB C, Sous-type H5N1 du virus de la grippe A (génétique), Sous-type H5N1 du virus de la grippe A (immunologie), Sous-type H5N1 du virus de la grippe A (pathogénicité), Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Vaccins antigrippaux (usage thérapeutique), Vaccins inactivés (génétique), Vaccins inactivés (immunologie).
- MESH :
- administration et posologie : Vaccins antigrippaux.
- génétique : ARN double brin, ARN viral, Anticorps antiviraux, Grippe chez les oiseaux, Récepteur de type Toll-3, Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Vaccins inactivés.
- immunologie : Anticorps antiviraux, Grippe chez les oiseaux, Grippe humaine, Sous-type H5N1 du virus de la grippe A, Vaccins antigrippaux, Vaccins inactivés.
- pathogénicité : Sous-type H5N1 du virus de la grippe A.
- usage thérapeutique : Vaccins antigrippaux.
- virologie : Grippe chez les oiseaux.
- épidémiologie : Grippe humaine.
- Administration par voie nasale, Animaux, Flambées de maladies, Humains, Mâle, Oiseaux, Réplication virale, Souris, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Administration, Intranasal, Animals, Antibodies, Viral (genetics), Antibodies, Viral (immunology), Birds, Disease Outbreaks, Humans, Influenza A Virus, H5N1 Subtype (genetics), Influenza A Virus, H5N1 Subtype (immunology), Influenza A Virus, H5N1 Subtype (pathogenicity), Influenza Vaccines (administration & dosage), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Influenza Vaccines (therapeutic use), Influenza in Birds (genetics), Influenza in Birds (immunology), Influenza in Birds (virology), Influenza, Human (epidemiology), Influenza, Human (immunology), Male, Mice, Mice, Inbred BALB C, RNA, Double-Stranded (genetics), RNA, Viral (genetics), Toll-Like Receptor 3 (genetics), Vaccines, Inactivated (genetics), Vaccines, Inactivated (immunology), Virus Replication.
- MESH :
- chemical , administration & dosage : Influenza Vaccines.
- chemical , genetics : Antibodies, Viral, Influenza Vaccines, RNA, Double-Stranded, RNA, Viral, Toll-Like Receptor 3, Vaccines, Inactivated.
- chemical , immunology : Antibodies, Viral, Influenza Vaccines, Vaccines, Inactivated.
- epidemiology : Influenza, Human.
- genetics : Influenza A Virus, H5N1 Subtype, Influenza in Birds.
- immunology : Influenza A Virus, H5N1 Subtype, Influenza in Birds, Influenza, Human.
- pathogenicity : Influenza A Virus, H5N1 Subtype.
- chemical , therapeutic use : Influenza Vaccines.
- virology : Influenza in Birds.
- Administration, Intranasal, Animals, Birds, Disease Outbreaks, Humans, Male, Mice, Mice, Inbred BALB C, Virus Replication.
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 of neuraminidase 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.
Url:
DOI: 10.1016/j.vaccine.2008.12.048
PubMed: 19150474
PubMed Central: 7115584
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PMC:7115584Le document en format XML
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<term>Disease Outbreaks</term>
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<term>Influenza A Virus, H5N1 Subtype (genetics)</term>
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<front><div type="abstract" xml:lang="en"><p>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 of neuraminidase 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.</p>
</div>
</front>
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