PandemieGrippaleV1, Ncbi, Curation, bibRecord, 001923

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Identifieur interne : 001923 ( Ncbi/Curation ); précédent : 001922; suivant : 001924

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Auteurs : Attapon Kamlangdee [États-Unis] ; Brock Kingstad-Bakke [États-Unis] ; Tavis K. Anderson [États-Unis] ; Tony L. Goldberg [États-Unis] ; Jorge E. Osorio [États-Unis]

Source :

Journal of Virology [ 0022-538X ] ; 2014.

RBID : PMC:4249068

Descripteurs français

English descriptors

KwdEn :
- Animals, Antibodies, Neutralizing (blood), Antibodies, Viral (blood), CD4-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (immunology), Cross Protection, Disease Models, Animal, Drug Carriers (administration & dosage), Genetic Vectors, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans, Influenza A Virus, H1N1 Subtype (immunology), Influenza A Virus, H5N1 Subtype (genetics), Influenza A Virus, H5N1 Subtype (immunology), Influenza Vaccines (administration & dosage), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Mice, Inbred BALB C, Orthomyxoviridae Infections (prevention & control), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (immunology), Survival Analysis, Vaccination (methods), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Vaccinia virus (genetics).
MESH :
- chemical , administration & dosage : Drug Carriers, Influenza Vaccines, Vaccines, Synthetic.
- chemical , blood : Antibodies, Neutralizing, Antibodies, Viral.
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Recombinant Fusion Proteins, Vaccines, Synthetic.
- genetics : Influenza A Virus, H5N1 Subtype, Vaccinia virus.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Hemagglutinin Glycoproteins, Influenza Virus, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype, Influenza Vaccines, Recombinant Fusion Proteins, Vaccines, Synthetic.
- methods : Vaccination.
- prevention & control : Orthomyxoviridae Infections.
- Animals, Cross Protection, Disease Models, Animal, Genetic Vectors, Humans, Mice, Inbred BALB C, Survival Analysis.

Abstract

ABSTRACT

A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4⁺ and CD8⁺ T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity.

IMPORTANCE Influenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel in silico mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249068

DOI: 10.1128/JVI.01532-14
PubMed: 25210173
PubMed Central: 4249068

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Le document en format XML

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<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Cross Protection</term>
<term>Disease Models, Animal</term>
<term>Drug Carriers (administration & dosage)</term>
<term>Genetic Vectors</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
<term>Humans</term>
<term>Influenza A Virus, H1N1 Subtype (immunology)</term>
<term>Influenza A Virus, H5N1 Subtype (genetics)</term>
<term>Influenza A Virus, H5N1 Subtype (immunology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Mice, Inbred BALB C</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
<term>Recombinant Fusion Proteins (genetics)</term>
<term>Recombinant Fusion Proteins (immunology)</term>
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<term>Anticorps neutralisants (sang)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term>
<term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protection croisée</term>
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<term>Protéines de fusion recombinantes (immunologie)</term>
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<term>Sous-type H5N1 du virus de la grippe A (immunologie)</term>
<term>Vaccination ()</term>
<term>Vaccins antigrippaux (administration et posologie)</term>
<term>Vaccins antigrippaux (génétique)</term>
<term>Vaccins antigrippaux (immunologie)</term>
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<term>Influenza Vaccines</term>
<term>Vaccines, Synthetic</term>
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<term>Antibodies, Viral</term>
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<term>Influenza Vaccines</term>
<term>Recombinant Fusion Proteins</term>
<term>Vaccines, Synthetic</term>
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<term>Vaccins synthétiques</term>
<term>Vecteurs de médicaments</term>
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<term>Vaccins antigrippaux</term>
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<term>Lymphocytes T CD8+</term>
<term>Protéines de fusion recombinantes</term>
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<term>Sous-type H5N1 du virus de la grippe A</term>
<term>Vaccins antigrippaux</term>
<term>Vaccins synthétiques</term>
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<term>CD8-Positive T-Lymphocytes</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus</term>
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza A Virus, H5N1 Subtype</term>
<term>Influenza Vaccines</term>
<term>Recombinant Fusion Proteins</term>
<term>Vaccines, Synthetic</term>
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<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Vaccination</term>
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<term>Anticorps neutralisants</term>
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<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cross Protection</term>
<term>Disease Models, Animal</term>
<term>Genetic Vectors</term>
<term>Humans</term>
<term>Mice, Inbred BALB C</term>
<term>Survival Analysis</term>
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<keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term>
<term>Animaux</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae</term>
<term>Modèles animaux de maladie humaine</term>
<term>Protection croisée</term>
<term>Souris de lignée BALB C</term>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated <italic>in silico</italic>
 using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection postvaccination. Both neutralizing antibodies and antigen-specific CD4<sup>+</sup>
 and CD8<sup>+</sup>
 T cells were still detected at 5 months postvaccination, suggesting that MVA-H5M provides long-lasting immunity.</p>
<p><bold>IMPORTANCE</bold>
 Influenza viruses infect a billion people and cause up to 500,000 deaths every year. A major problem in combating influenza is the lack of broadly effective vaccines. One solution from the field of human immunodeficiency virus vaccinology involves a novel <italic>in silico</italic>
 mosaic approach that has been shown to provide broad and robust protection against highly variable viruses. Unlike a consensus algorithm which picks the most frequent residue at each position, the mosaic method chooses the most frequent T-cell epitopes and combines them to form a synthetic antigen. These studies demonstrated that a mosaic influenza virus H5 hemagglutinin expressed by a viral vector can elicit full protection against diverse H5N1 challenges as well as induce broader immunity than a wild-type hemagglutinin.</p>
</div>
</front>
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Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

Broad Protection against Avian Influenza Virus by Using a Modified Vaccinia Ankara Virus Expressing a Mosaic Hemagglutinin Gene

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