Stalking influenza by vaccination with pre-fusion headless HA mini-stem.
Identifieur interne : 000B52 ( Main/Exploration ); précédent : 000B51; suivant : 000B53Stalking influenza by vaccination with pre-fusion headless HA mini-stem.
Auteurs : Sophie A. Valkenburg [Hong Kong] ; V Vamsee Aditya Mallajosyula [Inde] ; Olive T W. Li [Hong Kong] ; Alex W H. Chin [Hong Kong] ; George Carnell [Royaume-Uni] ; Nigel Temperton [Royaume-Uni] ; Raghavan Varadarajan [Inde] ; Leo L M. Poon [Hong Kong]Source :
- Scientific reports [ 2045-2322 ] ; 2016.
Descripteurs français
- KwdFr :
- Analyse de survie, Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Femelle, Glycoprotéine hémagglutinine du virus influenza (génétique), Glycoprotéine hémagglutinine du virus influenza (immunologie), Grippe humaine (), Humains, Immunisation passive, Infections à Orthomyxoviridae (), Liaison aux protéines, Modèles animaux de maladie humaine, Multimérisation de protéines, Pliage des protéines, Protéines recombinantes (génétique), Protéines recombinantes (immunologie), Résultat thérapeutique, Souris de lignée BALB C, Stabilité de médicament, Vaccins antigrippaux (administration et posologie), Vaccins antigrippaux (génétique), Vaccins antigrippaux (immunologie), Vaccins synthétiques (administration et posologie), Vaccins synthétiques (génétique), Vaccins synthétiques (immunologie).
- MESH :
- administration et posologie : Vaccins antigrippaux, Vaccins synthétiques.
- génétique : Glycoprotéine hémagglutinine du virus influenza, Protéines recombinantes, Vaccins antigrippaux, Vaccins synthétiques.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Glycoprotéine hémagglutinine du virus influenza, Protéines recombinantes, Vaccins antigrippaux, Vaccins synthétiques.
- Analyse de survie, Animaux, Femelle, Grippe humaine, Humains, Immunisation passive, Infections à Orthomyxoviridae, Liaison aux protéines, Modèles animaux de maladie humaine, Multimérisation de protéines, Pliage des protéines, Résultat thérapeutique, Souris de lignée BALB C, Stabilité de médicament.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Disease Models, Animal, Drug Stability, Female, Hemagglutinin Glycoproteins, Influenza Virus (genetics), Hemagglutinin Glycoproteins, Influenza Virus (immunology), Humans, Immunization, Passive, Influenza Vaccines (administration & dosage), Influenza Vaccines (genetics), Influenza Vaccines (immunology), Influenza, Human (prevention & control), Mice, Inbred BALB C, Orthomyxoviridae Infections (prevention & control), Protein Binding, Protein Folding, Protein Multimerization, Recombinant Proteins (genetics), Recombinant Proteins (immunology), Survival Analysis, Treatment Outcome, Vaccines, Synthetic (administration & dosage), Vaccines, Synthetic (genetics), Vaccines, Synthetic (immunology).
- MESH :
- chemical , administration & dosage : Influenza Vaccines, Vaccines, Synthetic.
- chemical , genetics : Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Recombinant Proteins, Vaccines, Synthetic.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Hemagglutinin Glycoproteins, Influenza Virus, Influenza Vaccines, Recombinant Proteins, Vaccines, Synthetic.
- prevention & control : Influenza, Human, Orthomyxoviridae Infections.
- Animals, Disease Models, Animal, Drug Stability, Female, Humans, Immunization, Passive, Mice, Inbred BALB C, Protein Binding, Protein Folding, Protein Multimerization, Survival Analysis, Treatment Outcome.
Abstract
Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.
DOI: 10.1038/srep22666
PubMed: 26947245
Affiliations:
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Le document en format XML
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Valkenburg</name><affiliation wicri:level="1"><nlm:affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong</wicri:regionArea><wicri:noRegion>The University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Mallajosyula, V Vamsee Aditya" sort="Mallajosyula, V Vamsee Aditya" uniqKey="Mallajosyula V" first="V Vamsee Aditya" last="Mallajosyula">V Vamsee Aditya Mallajosyula</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Biophysics Unit, Indian Institute of Science, Bangalore</wicri:regionArea><wicri:noRegion>Bangalore</wicri:noRegion></affiliation></author><author><name sortKey="Li, Olive T W" sort="Li, Olive T W" uniqKey="Li O" first="Olive T W" last="Li">Olive T W. 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Valkenburg</name><affiliation wicri:level="1"><nlm:affiliation>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong</wicri:regionArea><wicri:noRegion>The University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Mallajosyula, V Vamsee Aditya" sort="Mallajosyula, V Vamsee Aditya" uniqKey="Mallajosyula V" first="V Vamsee Aditya" last="Mallajosyula">V Vamsee Aditya Mallajosyula</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Biophysics Unit, Indian Institute of Science, Bangalore</wicri:regionArea><wicri:noRegion>Bangalore</wicri:noRegion></affiliation></author><author><name sortKey="Li, Olive T W" sort="Li, Olive T W" uniqKey="Li O" first="Olive T W" last="Li">Olive T W. Li</name><affiliation wicri:level="1"><nlm:affiliation>Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Center of Influenza Research and School of Public Health, The University of Hong Kong</wicri:regionArea><wicri:noRegion>The University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chin, Alex W H" sort="Chin, Alex W H" uniqKey="Chin A" first="Alex W H" last="Chin">Alex W H. Chin</name><affiliation wicri:level="1"><nlm:affiliation>Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Center of Influenza Research and School of Public Health, The University of Hong Kong</wicri:regionArea><wicri:noRegion>The University of Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Carnell, George" sort="Carnell, George" uniqKey="Carnell G" first="George" last="Carnell">George Carnell</name><affiliation wicri:level="1"><nlm:affiliation>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent</wicri:regionArea><wicri:noRegion>Kent</wicri:noRegion></affiliation></author><author><name sortKey="Temperton, Nigel" sort="Temperton, Nigel" uniqKey="Temperton N" first="Nigel" last="Temperton">Nigel Temperton</name><affiliation wicri:level="1"><nlm:affiliation>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Viral Pseudotype Unit, School of Pharmacy, University of Kent, Kent</wicri:regionArea><wicri:noRegion>Kent</wicri:noRegion></affiliation></author><author><name sortKey="Varadarajan, Raghavan" sort="Varadarajan, Raghavan" uniqKey="Varadarajan R" first="Raghavan" last="Varadarajan">Raghavan Varadarajan</name><affiliation wicri:level="1"><nlm:affiliation>Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Molecular Biophysics Unit, Indian Institute of Science, Bangalore</wicri:regionArea><wicri:noRegion>Bangalore</wicri:noRegion></affiliation></author><author><name sortKey="Poon, Leo L M" sort="Poon, Leo L M" uniqKey="Poon L" first="Leo L M" last="Poon">Leo L M. Poon</name><affiliation wicri:level="1"><nlm:affiliation>Center of Influenza Research and School of Public Health, The University of Hong Kong, Hong Kong.</nlm:affiliation><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Center of Influenza Research and School of Public Health, The University of Hong Kong</wicri:regionArea><wicri:noRegion>The University of Hong Kong</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Disease Models, Animal</term><term>Drug Stability</term><term>Female</term><term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term><term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term><term>Humans</term><term>Immunization, Passive</term><term>Influenza Vaccines (administration & dosage)</term><term>Influenza Vaccines (genetics)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (prevention & control)</term><term>Mice, Inbred BALB C</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Protein Binding</term><term>Protein Folding</term><term>Protein Multimerization</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (immunology)</term><term>Survival Analysis</term><term>Treatment Outcome</term><term>Vaccines, Synthetic (administration & dosage)</term><term>Vaccines, Synthetic (genetics)</term><term>Vaccines, Synthetic (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps neutralisants (immunologie)</term><term>Femelle</term><term>Glycoprotéine hémagglutinine du virus influenza (génétique)</term><term>Glycoprotéine hémagglutinine du virus influenza (immunologie)</term><term>Grippe humaine ()</term><term>Humains</term><term>Immunisation passive</term><term>Infections à Orthomyxoviridae ()</term><term>Liaison aux protéines</term><term>Modèles animaux de maladie humaine</term><term>Multimérisation de protéines</term><term>Pliage des protéines</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (immunologie)</term><term>Résultat thérapeutique</term><term>Souris de lignée BALB C</term><term>Stabilité de médicament</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></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Influenza Vaccines</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Influenza Vaccines</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Hemagglutinin Glycoproteins, Influenza Virus</term><term>Influenza Vaccines</term><term>Recombinant Proteins</term><term>Vaccines, Synthetic</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Protéines recombinantes</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Glycoprotéine hémagglutinine du virus influenza</term><term>Protéines recombinantes</term><term>Vaccins antigrippaux</term><term>Vaccins synthétiques</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Influenza, Human</term><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Drug Stability</term><term>Female</term><term>Humans</term><term>Immunization, Passive</term><term>Mice, Inbred BALB C</term><term>Protein Binding</term><term>Protein Folding</term><term>Protein Multimerization</term><term>Survival Analysis</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term><term>Animaux</term><term>Femelle</term><term>Grippe humaine</term><term>Humains</term><term>Immunisation passive</term><term>Infections à Orthomyxoviridae</term><term>Liaison aux protéines</term><term>Modèles animaux de maladie humaine</term><term>Multimérisation de protéines</term><term>Pliage des protéines</term><term>Résultat thérapeutique</term><term>Souris de lignée BALB C</term><term>Stabilité de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>Inde</li><li>Royaume-Uni</li></country></list><tree><country name="Hong Kong"><noRegion><name sortKey="Valkenburg, Sophie A" sort="Valkenburg, Sophie A" uniqKey="Valkenburg S" first="Sophie A" last="Valkenburg">Sophie A. Valkenburg</name></noRegion><name sortKey="Chin, Alex W H" sort="Chin, Alex W H" uniqKey="Chin A" first="Alex W H" last="Chin">Alex W H. Chin</name><name sortKey="Li, Olive T W" sort="Li, Olive T W" uniqKey="Li O" first="Olive T W" last="Li">Olive T W. Li</name><name sortKey="Poon, Leo L M" sort="Poon, Leo L M" uniqKey="Poon L" first="Leo L M" last="Poon">Leo L M. Poon</name></country><country name="Inde"><noRegion><name sortKey="Mallajosyula, V Vamsee Aditya" sort="Mallajosyula, V Vamsee Aditya" uniqKey="Mallajosyula V" first="V Vamsee Aditya" last="Mallajosyula">V Vamsee Aditya Mallajosyula</name></noRegion><name sortKey="Varadarajan, Raghavan" sort="Varadarajan, Raghavan" uniqKey="Varadarajan R" first="Raghavan" last="Varadarajan">Raghavan Varadarajan</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Carnell, George" sort="Carnell, George" uniqKey="Carnell G" first="George" last="Carnell">George Carnell</name></noRegion><name sortKey="Temperton, Nigel" sort="Temperton, Nigel" uniqKey="Temperton N" first="Nigel" last="Temperton">Nigel Temperton</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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