Alternative Live-Attenuated Influenza Vaccines Based on Modifications in the Polymerase Genes Protect against Epidemic and Pandemic Flu▿
Identifieur interne : 000F12 ( Main/Merge ); précédent : 000F11; suivant : 000F13Alternative Live-Attenuated Influenza Vaccines Based on Modifications in the Polymerase Genes Protect against Epidemic and Pandemic Flu▿
Auteurs : Alicia Sol Rzano [États-Unis] ; Jianqiang Ye [États-Unis] ; Daniel R. Pérez [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Dose létale 50, Femelle, Glycoprotéine hémagglutinine du virus influenza (génétique), Humains, Infections à Orthomyxoviridae (anatomopathologie), Infections à Orthomyxoviridae (immunologie), Infections à Orthomyxoviridae (virologie), Méthode des plages virales, Poids du corps, Poumon (virologie), Protéines virales (génétique), RNA replicase (génétique), Souris, Souris de lignée BALB C, Souris de lignée DBA, Sous-type H1N1 du virus de la grippe A (immunologie), Sous-type H3N2 du virus de la grippe A (génétique), Sous-type H3N2 du virus de la grippe A (immunologie), Vaccins antigrippaux (immunologie), Vaccins atténués (immunologie).
- MESH :
- anatomopathologie : Infections à Orthomyxoviridae.
- génétique : Glycoprotéine hémagglutinine du virus influenza, Protéines virales, RNA replicase, Sous-type H3N2 du virus de la grippe A.
- immunologie : Infections à Orthomyxoviridae, Sous-type H1N1 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Vaccins antigrippaux, Vaccins atténués.
- virologie : Infections à Orthomyxoviridae, Poumon.
- Animaux, Dose létale 50, Femelle, Humains, Méthode des plages virales, Poids du corps, Souris, Souris de lignée BALB C, Souris de lignée DBA.
English descriptors
- KwdEn :
- Animals, Body Weight, Female, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Humans, Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H3N2 Subtype (genetics), Influenza A Virus, H3N2 Subtype (immunology), Influenza Vaccines (immunology), Lethal Dose 50, Lung (virology), Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (pathology), Orthomyxoviridae Infections (virology), RNA Replicase (genetics), Vaccines, Attenuated (immunology), Viral Plaque Assay, Viral Proteins (genetics).
- MESH :
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus, RNA Replicase, Viral Proteins.
- genetics : Influenza A Virus, H3N2 Subtype.
- immunology : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza Vaccines, Orthomyxoviridae Infections, Vaccines, Attenuated.
- pathology : Orthomyxoviridae Infections.
- virology : Lung, Orthomyxoviridae Infections.
- Animals, Body Weight, Female, Humans, Lethal Dose 50, Mice, Mice, Inbred BALB C, Mice, Inbred DBA, Viral Plaque Assay.
Abstract
Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza vaccination is the most effective means for disease prevention. We have previously shown that mutations in the PB1 and PB2 genes of the live-attenuated influenza vaccine (LAIV) from the cold-adapted (
Url:
DOI: 10.1128/JVI.00101-10
PubMed: 20181702
PubMed Central: 2863734
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PMC:2863734Le document en format XML
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<term>Body Weight</term>
<term>Female</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype (immunology)</term>
<term>Influenza A Virus, H3N2 Subtype (genetics)</term>
<term>Influenza A Virus, H3N2 Subtype (immunology)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Lethal Dose 50</term>
<term>Lung (virology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Mice, Inbred DBA</term>
<term>Orthomyxoviridae Infections (immunology)</term>
<term>Orthomyxoviridae Infections (pathology)</term>
<term>Orthomyxoviridae Infections (virology)</term>
<term>RNA Replicase (genetics)</term>
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<term>Viral Plaque Assay</term>
<term>Viral Proteins (genetics)</term>
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<term>Dose létale 50</term>
<term>Femelle</term>
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<term>Humains</term>
<term>Infections à Orthomyxoviridae (anatomopathologie)</term>
<term>Infections à Orthomyxoviridae (immunologie)</term>
<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Méthode des plages virales</term>
<term>Poids du corps</term>
<term>Poumon (virologie)</term>
<term>Protéines virales (génétique)</term>
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<term>Souris de lignée BALB C</term>
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<term>Sous-type H3N2 du virus de la grippe A (génétique)</term>
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<term>Vaccins antigrippaux (immunologie)</term>
<term>Vaccins atténués (immunologie)</term>
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<term>Sous-type H3N2 du virus de la grippe A</term>
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<term>Sous-type H1N1 du virus de la grippe A</term>
<term>Sous-type H3N2 du virus de la grippe A</term>
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<front><div type="abstract" xml:lang="en"><p>Human influenza is a seasonal disease associated with significant morbidity and mortality. Influenza vaccination is the most effective means for disease prevention. We have previously shown that mutations in the PB1 and PB2 genes of the live-attenuated influenza vaccine (LAIV) from the cold-adapted (<italic>ca</italic>
) influenza virus A/Ann Arbor/6/60 (H2N2) could be transferred to avian influenza viruses and produce partially attenuated viruses. We also demonstrated that avian influenza viruses carrying the PB1 and PB2 mutations could be further attenuated by stably introducing a hemagglutinin (HA) epitope tag in the PB1 gene. In this work, we wanted to determine whether these modifications would also result in attenuation of a so-called triple reassortant (TR) swine influenza virus (SIV). Thus, the TR influenza A/swine/Wisconsin/14094/99 (H3N2) virus was generated by reverse genetics and subsequently mutated in the PB1 and PB2 genes. Here we show that a combination of mutations in this TR backbone results in an attenuated virus <italic>in vitro</italic>
and <italic>in vivo</italic>
. Furthermore, we show the potential of our TR backbone as a vaccine that provides protection against the 2009 swine-origin pandemic influenza H1N1 virus (S-OIV) when carrying the surface of a classical swine strain. We propose that the availability of alternative backbones to the conventional <italic>ca</italic>
A/Ann Arbor/6/60 LAIV strain could also be useful in epidemic and pandemic influenza and should be considered for influenza vaccine development. In addition, our data provide evidence that the use of these alternative backbones could potentially circumvent the effects of original antigenic sin (OAS) in certain circumstances.</p>
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