Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.
Identifieur interne : 000577 ( Main/Exploration ); précédent : 000576; suivant : 000578Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.
Auteurs : Liudmila M. Tsybalova [Russie] ; Liudmila A. Stepanova [Russie] ; Victor V. Kuprianov [Russie] ; Elena A. Blokhina [Russie] ; Marina V. Potapchuk [Russie] ; Alexander V. Korotkov [Russie] ; Andrey N. Gorshkov [Russie] ; Marina A. Kasyanenko [Russie] ; Nikolai V. Ravin [Russie] ; Oleg I. Kiselev [Russie]Source :
- Vaccine [ 1873-2518 ] ; 2015.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Anticorps antiviraux (analyse), Anticorps antiviraux (sang), Antigènes de la nucléocapside du virus de l'hépatite virale B (génétique), Charge virale, Escherichia coli (génétique), Expression des gènes, Femelle, Immunoglobuline G (analyse), Immunoglobuline G (sang), Infections à Orthomyxoviridae (), Liquide de lavage bronchoalvéolaire (immunologie), Lymphocytes T (immunologie), Modèles animaux de maladie humaine, Mutagenèse par insertion, Poumon (virologie), Protection croisée, Protéines de fusion recombinantes (génétique), Protéines de fusion recombinantes (immunologie), Protéines de la matrice virale (génétique), Protéines de la matrice virale (immunologie), Réactions croisées, Sang (immunologie), Souris de lignée BALB C, Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Vaccins synthétiques (administration et posologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie), Vaccins à pseudo-particules virales (administration et posologie), Vaccins à pseudo-particules virales (génétique), Vaccins à pseudo-particules virales (immunologie), Épitopes (génétique), Épitopes (immunologie).
- MESH :
- administration et posologie : Vaccins antigrippaux, Vaccins synthétiques, Vaccins à pseudo-particules virales.
- analyse : Anticorps antiviraux, Immunoglobuline G.
- génétique : Antigènes de la nucléocapside du virus de l'hépatite virale B, Escherichia coli, Protéines de fusion recombinantes, Protéines de la matrice virale, Vaccins antigrippaux, Vaccins synthétiques, Vaccins à pseudo-particules virales, Épitopes.
- immunologie : Liquide de lavage bronchoalvéolaire, Lymphocytes T, Protéines de fusion recombinantes, Protéines de la matrice virale, Sang, Vaccins antigrippaux, Vaccins synthétiques, Vaccins à pseudo-particules virales, Épitopes.
- sang : Anticorps antiviraux, Immunoglobuline G.
- virologie : Poumon.
- Analyse de survie, Animaux, Charge virale, Expression des gènes, Femelle, Infections à Orthomyxoviridae, Modèles animaux de maladie humaine, Mutagenèse par insertion, Protection croisée, Réactions croisées, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (analysis), Antibodies, Viral (blood), Blood (immunology), Bronchoalveolar Lavage Fluid (immunology), Cross Protection, Cross Reactions, Disease Models, Animal, Epitopes (genetics), Epitopes (immunology), Escherichia coli (genetics), Female, Gene Expression, Hepatitis B Core Antigens (genetics), Immunoglobulin G (analysis), Immunoglobulin G (blood), Influenza Vaccines (administration & dosage), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Lung (virology), Mice, Inbred BALB C, Mutagenesis, Insertional, Orthomyxoviridae Infections (prevention & control), Recombinant Fusion Proteins (genetics), Recombinant Fusion Proteins (immunology), Survival Analysis, T-Lymphocytes (immunology), Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology), Vaccines, Virus-Like Particle (administration & dosage), Vaccines, Virus-Like Particle (genetics), Vaccines, Virus-Like Particle (immunology), Viral Load, Viral Matrix Proteins (genetics), Viral Matrix Proteins (immunology).
- MESH :
- chemical , administration & dosage : Influenza Vaccines, Vaccines, Synthetic, Vaccines, Virus-Like Particle.
- chemical , analysis : Antibodies, Viral, Immunoglobulin G.
- chemical , blood : Antibodies, Viral, Immunoglobulin G.
- chemical , genetics : Epitopes, Hepatitis B Core Antigens, Influenza Vaccines, Recombinant Fusion Proteins, Vaccines, Synthetic, Vaccines, Virus-Like Particle, Viral Matrix Proteins.
- genetics : Escherichia coli.
- immunology : Blood, Bronchoalveolar Lavage Fluid, Epitopes, Influenza Vaccines, Recombinant Fusion Proteins, T-Lymphocytes, Vaccines, Synthetic, Vaccines, Virus-Like Particle, Viral Matrix Proteins.
- prevention & control : Orthomyxoviridae Infections.
- virology : Lung.
- Animals, Cross Protection, Cross Reactions, Disease Models, Animal, Female, Gene Expression, Mice, Inbred BALB C, Mutagenesis, Insertional, Survival Analysis, Viral Load.
Abstract
A long-term objective when designing influenza vaccines is to create one with broad cross-reactivity that will provide effective control over influenza, no matter which strain has caused the disease. Here we summarize the results from an investigation into the immunogenic and protective capacities inherent in variations of a recombinant protein, HBc/4M2e. This protein contains four copies of the ectodomain from the influenza virus protein M2 (M2e) fused within the immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of this basic design include preparations containing M2e from the consensus human influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a combination of two copies from human and two copies from avian influenza viruses. Intramuscular delivery in mice with preparations containing four identical copies of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also provoked the formation of memory T-cells and antibodies were retained in the blood sera for a significant period of time post immunization. Furthermore, these preparations prevented the death of 75-100% of animals, which were challenged with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral replication within the lungs. Moreover, HBc particles carrying only "human" or "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the particles carrying both "human" and "avian" M2e this effect was much weaker, especially in relation to influenza virus A/H5N1. It is apparent from this work that to quickly produce vaccine for a pandemic it would be necessary to have several variations of a recombinant protein, containing four copies of M2e (each one against a group of likely influenza virus strains) with these relevant constructs housed within a comprehensive collection Escherichia coli-producers and maintained ready for use.
DOI: 10.1016/j.vaccine.2015.04.073
PubMed: 25976545
Affiliations:
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Tsybalova</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia. Electronic address: sovet@influenza.spb.ru.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Stepanova, Liudmila A" sort="Stepanova, Liudmila A" uniqKey="Stepanova L" first="Liudmila A" last="Stepanova">Liudmila A. Stepanova</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Kuprianov, Victor V" sort="Kuprianov, Victor V" uniqKey="Kuprianov V" first="Victor V" last="Kuprianov">Victor V. Kuprianov</name><affiliation wicri:level="3"><nlm:affiliation>Centre "Bioengineering", Russian Academy of Science, Moscow, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Centre "Bioengineering", Russian Academy of Science, Moscow</wicri:regionArea><placeName><settlement type="city">Moscou</settlement><region>District fédéral central</region></placeName></affiliation></author><author><name sortKey="Blokhina, Elena A" sort="Blokhina, Elena A" uniqKey="Blokhina E" first="Elena A" last="Blokhina">Elena A. Blokhina</name><affiliation wicri:level="3"><nlm:affiliation>Centre "Bioengineering", Russian Academy of Science, Moscow, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Centre "Bioengineering", Russian Academy of Science, Moscow</wicri:regionArea><placeName><settlement type="city">Moscou</settlement><region>District fédéral central</region></placeName></affiliation></author><author><name sortKey="Potapchuk, Marina V" sort="Potapchuk, Marina V" uniqKey="Potapchuk M" first="Marina V" last="Potapchuk">Marina V. Potapchuk</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Korotkov, Alexander V" sort="Korotkov, Alexander V" uniqKey="Korotkov A" first="Alexander V" last="Korotkov">Alexander V. Korotkov</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Gorshkov, Andrey N" sort="Gorshkov, Andrey N" uniqKey="Gorshkov A" first="Andrey N" last="Gorshkov">Andrey N. Gorshkov</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Kasyanenko, Marina A" sort="Kasyanenko, Marina A" uniqKey="Kasyanenko M" first="Marina A" last="Kasyanenko">Marina A. Kasyanenko</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author><author><name sortKey="Ravin, Nikolai V" sort="Ravin, Nikolai V" uniqKey="Ravin N" first="Nikolai V" last="Ravin">Nikolai V. Ravin</name><affiliation wicri:level="3"><nlm:affiliation>Centre "Bioengineering", Russian Academy of Science, Moscow, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Centre "Bioengineering", Russian Academy of Science, Moscow</wicri:regionArea><placeName><settlement type="city">Moscou</settlement><region>District fédéral central</region></placeName></affiliation></author><author><name sortKey="Kiselev, Oleg I" sort="Kiselev, Oleg I" uniqKey="Kiselev O" first="Oleg I" last="Kiselev">Oleg I. Kiselev</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg, Russia.</nlm:affiliation><country xml:lang="fr">Russie</country><wicri:regionArea>Research Institute of Influenza, Russian Federation Ministry of Health, St. Petersburg</wicri:regionArea><wicri:noRegion>St. Petersburg</wicri:noRegion></affiliation></author></analytic><series><title level="j">Vaccine</title><idno type="eISSN">1873-2518</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Viral (analysis)</term><term>Antibodies, Viral (blood)</term><term>Blood (immunology)</term><term>Bronchoalveolar Lavage Fluid (immunology)</term><term>Cross Protection</term><term>Cross Reactions</term><term>Disease Models, Animal</term><term>Epitopes (genetics)</term><term>Epitopes (immunology)</term><term>Escherichia coli (genetics)</term><term>Female</term><term>Gene Expression</term><term>Hepatitis B Core Antigens (genetics)</term><term>Immunoglobulin G (analysis)</term><term>Immunoglobulin G (blood)</term><term>Influenza Vaccines (administration & dosage)</term><term>Influenza Vaccines (genetics)</term><term>Influenza Vaccines (immunology)</term><term>Lung (virology)</term><term>Mice, Inbred BALB C</term><term>Mutagenesis, Insertional</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Recombinant Fusion Proteins (genetics)</term><term>Recombinant Fusion Proteins (immunology)</term><term>Survival Analysis</term><term>T-Lymphocytes (immunology)</term><term>Vaccines, Synthetic (administration & dosage)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term><term>Vaccines, Virus-Like Particle (administration & dosage)</term><term>Vaccines, Virus-Like Particle (genetics)</term><term>Vaccines, Virus-Like Particle (immunology)</term><term>Viral Load</term><term>Viral Matrix Proteins (genetics)</term><term>Viral Matrix Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Anticorps antiviraux (analyse)</term><term>Anticorps antiviraux (sang)</term><term>Antigènes de la nucléocapside du virus de l'hépatite virale B (génétique)</term><term>Charge virale</term><term>Escherichia coli (génétique)</term><term>Expression des gènes</term><term>Femelle</term><term>Immunoglobuline G (analyse)</term><term>Immunoglobuline G (sang)</term><term>Infections à Orthomyxoviridae ()</term><term>Liquide de lavage bronchoalvéolaire (immunologie)</term><term>Lymphocytes T (immunologie)</term><term>Modèles animaux de maladie humaine</term><term>Mutagenèse par insertion</term><term>Poumon (virologie)</term><term>Protection croisée</term><term>Protéines de fusion recombinantes (génétique)</term><term>Protéines de fusion recombinantes (immunologie)</term><term>Protéines de la matrice virale (génétique)</term><term>Protéines de la matrice virale (immunologie)</term><term>Réactions croisées</term><term>Sang (immunologie)</term><term>Souris de lignée BALB C</term><term>Vaccins antigrippaux (administration et posologie)</term><term>Vaccins antigrippaux (génétique)</term><term>Vaccins antigrippaux (immunologie)</term><term>Vaccins synthétiques (administration et posologie)</term><term>Vaccins synthétiques (génétique)</term><term>Vaccins synthétiques (immunologie)</term><term>Vaccins à pseudo-particules virales (administration et posologie)</term><term>Vaccins à pseudo-particules virales (génétique)</term><term>Vaccins à pseudo-particules virales (immunologie)</term><term>Épitopes (génétique)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Synthetic</term><term>Vaccines, Virus-Like Particle</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Antibodies, Viral</term><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antibodies, Viral</term><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Epitopes</term><term>Hepatitis B Core Antigens</term><term>Influenza Vaccines</term><term>Recombinant Fusion Proteins</term><term>Vaccines, Synthetic</term><term>Vaccines, Virus-Like Particle</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term><term>Vaccins à pseudo-particules virales</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Anticorps antiviraux</term><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes de la nucléocapside du virus de l'hépatite virale B</term><term>Escherichia coli</term><term>Protéines de fusion recombinantes</term><term>Protéines de la matrice virale</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term><term>Vaccins à pseudo-particules virales</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Liquide de lavage bronchoalvéolaire</term><term>Lymphocytes T</term><term>Protéines de fusion recombinantes</term><term>Protéines de la matrice virale</term><term>Sang</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term><term>Vaccins à pseudo-particules virales</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Blood</term><term>Bronchoalveolar Lavage Fluid</term><term>Epitopes</term><term>Influenza Vaccines</term><term>Recombinant Fusion Proteins</term><term>T-Lymphocytes</term><term>Vaccines, Synthetic</term><term>Vaccines, Virus-Like Particle</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cross Protection</term><term>Cross Reactions</term><term>Disease Models, Animal</term><term>Female</term><term>Gene Expression</term><term>Mice, Inbred BALB C</term><term>Mutagenesis, Insertional</term><term>Survival Analysis</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Charge virale</term><term>Expression des gènes</term><term>Femelle</term><term>Infections à Orthomyxoviridae</term><term>Modèles animaux de maladie humaine</term><term>Mutagenèse par insertion</term><term>Protection croisée</term><term>Réactions croisées</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A long-term objective when designing influenza vaccines is to create one with broad cross-reactivity that will provide effective control over influenza, no matter which strain has caused the disease. Here we summarize the results from an investigation into the immunogenic and protective capacities inherent in variations of a recombinant protein, HBc/4M2e. This protein contains four copies of the ectodomain from the influenza virus protein M2 (M2e) fused within the immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of this basic design include preparations containing M2e from the consensus human influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a combination of two copies from human and two copies from avian influenza viruses. Intramuscular delivery in mice with preparations containing four identical copies of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also provoked the formation of memory T-cells and antibodies were retained in the blood sera for a significant period of time post immunization. Furthermore, these preparations prevented the death of 75-100% of animals, which were challenged with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral replication within the lungs. Moreover, HBc particles carrying only "human" or "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the particles carrying both "human" and "avian" M2e this effect was much weaker, especially in relation to influenza virus A/H5N1. It is apparent from this work that to quickly produce vaccine for a pandemic it would be necessary to have several variations of a recombinant protein, containing four copies of M2e (each one against a group of likely influenza virus strains) with these relevant constructs housed within a comprehensive collection Escherichia coli-producers and maintained ready for use. </div></front></TEI><affiliations><list><country><li>Russie</li></country><region><li>District fédéral central</li></region><settlement><li>Moscou</li></settlement></list><tree><country name="Russie"><noRegion><name sortKey="Tsybalova, Liudmila M" sort="Tsybalova, Liudmila M" uniqKey="Tsybalova L" first="Liudmila M" last="Tsybalova">Liudmila M. Tsybalova</name></noRegion><name sortKey="Blokhina, Elena A" sort="Blokhina, Elena A" uniqKey="Blokhina E" first="Elena A" last="Blokhina">Elena A. Blokhina</name><name sortKey="Gorshkov, Andrey N" sort="Gorshkov, Andrey N" uniqKey="Gorshkov A" first="Andrey N" last="Gorshkov">Andrey N. Gorshkov</name><name sortKey="Kasyanenko, Marina A" sort="Kasyanenko, Marina A" uniqKey="Kasyanenko M" first="Marina A" last="Kasyanenko">Marina A. Kasyanenko</name><name sortKey="Kiselev, Oleg I" sort="Kiselev, Oleg I" uniqKey="Kiselev O" first="Oleg I" last="Kiselev">Oleg I. Kiselev</name><name sortKey="Korotkov, Alexander V" sort="Korotkov, Alexander V" uniqKey="Korotkov A" first="Alexander V" last="Korotkov">Alexander V. Korotkov</name><name sortKey="Kuprianov, Victor V" sort="Kuprianov, Victor V" uniqKey="Kuprianov V" first="Victor V" last="Kuprianov">Victor V. Kuprianov</name><name sortKey="Potapchuk, Marina V" sort="Potapchuk, Marina V" uniqKey="Potapchuk M" first="Marina V" last="Potapchuk">Marina V. Potapchuk</name><name sortKey="Ravin, Nikolai V" sort="Ravin, Nikolai V" uniqKey="Ravin N" first="Nikolai V" last="Ravin">Nikolai V. Ravin</name><name sortKey="Stepanova, Liudmila A" sort="Stepanova, Liudmila A" uniqKey="Stepanova L" first="Liudmila A" last="Stepanova">Liudmila A. Stepanova</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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