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Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

Identifieur interne : 002358 ( Ncbi/Merge ); précédent : 002357; suivant : 002359

Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

Auteurs : Ye V. Liu [États-Unis] ; Michael J. Massare [États-Unis] ; Dale L. Barnard [États-Unis] ; Thomas Kort [États-Unis] ; Margret Nathan [États-Unis] ; Lei Wang [États-Unis] ; Gale Smith [États-Unis]

Source :

RBID : PMC:3165014

Descripteurs français

English descriptors

Abstract

SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.


Url:
DOI: 10.1016/j.vaccine.2011.06.111
PubMed: 21762752
PubMed Central: 3165014

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PMC:3165014

Le document en format XML

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<p>SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.</p>
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<name sortKey="Liu, Ye V" sort="Liu, Ye V" uniqKey="Liu Y" first="Ye V." last="Liu">Ye V. Liu</name>
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<name sortKey="Kort, Thomas" sort="Kort, Thomas" uniqKey="Kort T" first="Thomas" last="Kort">Thomas Kort</name>
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<name sortKey="Nathan, Margret" sort="Nathan, Margret" uniqKey="Nathan M" first="Margret" last="Nathan">Margret Nathan</name>
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<name sortKey="Smith, Gale" sort="Smith, Gale" uniqKey="Smith G" first="Gale" last="Smith">Gale Smith</name>
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<author>
<name sortKey="Liu, Ye V" sort="Liu, Ye V" uniqKey="Liu Y" first="Ye V." last="Liu">Ye V. Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850</wicri:regionArea>
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<region type="state">Maryland</region>
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<name sortKey="Massare, Michael J" sort="Massare, Michael J" uniqKey="Massare M" first="Michael J." last="Massare">Michael J. Massare</name>
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<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Barnard, Dale L" sort="Barnard, Dale L" uniqKey="Barnard D" first="Dale L." last="Barnard">Dale L. Barnard</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0010">Institute for Antiviral Research, Utah State University, Logan, UT 84322, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute for Antiviral Research, Utah State University, Logan, UT 84322</wicri:regionArea>
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<region type="state">Utah</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Kort, Thomas" sort="Kort, Thomas" uniqKey="Kort T" first="Thomas" last="Kort">Thomas Kort</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author>
<name sortKey="Nathan, Margret" sort="Nathan, Margret" uniqKey="Nathan M" first="Margret" last="Nathan">Margret Nathan</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850</wicri:regionArea>
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<region type="state">Maryland</region>
</placeName>
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<author>
<name sortKey="Wang, Lei" sort="Wang, Lei" uniqKey="Wang L" first="Lei" last="Wang">Lei Wang</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
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</author>
<author>
<name sortKey="Smith, Gale" sort="Smith, Gale" uniqKey="Smith G" first="Gale" last="Smith">Gale Smith</name>
<affiliation wicri:level="2">
<nlm:aff id="aff0005">Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850, United States</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Novavax Inc., 9920 Belward Campus Drive, Rockville, MD 20850</wicri:regionArea>
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<region type="state">Maryland</region>
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<series>
<title level="j">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
<idno type="eISSN">1873-2518</idno>
<imprint>
<date when="2011">2011</date>
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<front>
<div type="abstract" xml:lang="en">
<p>SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.</p>
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<name sortKey="Smith, Gale" sort="Smith, Gale" uniqKey="Smith G" first="Gale" last="Smith">Gale Smith</name>
</author>
</analytic>
<series>
<title level="j">Vaccine</title>
<idno type="eISSN">1873-2518</idno>
<imprint>
<date when="2011" type="published">2011</date>
</imprint>
</series>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adjuvants, Immunologic (administration & dosage)</term>
<term>Aluminum Hydroxide (administration & dosage)</term>
<term>Animals</term>
<term>Antibodies, Neutralizing (blood)</term>
<term>Antibodies, Viral (blood)</term>
<term>Baculoviridae (genetics)</term>
<term>Body Weight</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Genetic Vectors</term>
<term>Insecta</term>
<term>Lung (virology)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (immunology)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Protein Multimerization</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (immunology)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>Rodent Diseases (prevention & control)</term>
<term>SARS Virus (genetics)</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Survival Analysis</term>
<term>Vaccines, Virosome (genetics)</term>
<term>Vaccines, Virosome (immunology)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
<term>Viral Envelope Proteins (metabolism)</term>
<term>Viral Load</term>
<term>Viral Matrix Proteins (genetics)</term>
<term>Viral Matrix Proteins (metabolism)</term>
<term>Viral Vaccines (genetics)</term>
<term>Viral Vaccines (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adjuvants immunologiques (administration et posologie)</term>
<term>Analyse de survie</term>
<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Anticorps neutralisants (sang)</term>
<term>Baculoviridae (génétique)</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (immunologie)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Hydroxyde d'aluminium (administration et posologie)</term>
<term>Maladies des rongeurs ()</term>
<term>Modèles animaux de maladie humaine</term>
<term>Multimérisation de protéines</term>
<term>Poids du corps</term>
<term>Poumon (virologie)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines de l'enveloppe virale (métabolisme)</term>
<term>Protéines de la matrice virale (génétique)</term>
<term>Protéines de la matrice virale (métabolisme)</term>
<term>Protéines recombinantes (génétique)</term>
<term>Protéines recombinantes (immunologie)</term>
<term>Protéines recombinantes (métabolisme)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère ()</term>
<term>Vaccins antiviraux (génétique)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins à virosomes (génétique)</term>
<term>Vaccins à virosomes (immunologie)</term>
<term>Vecteurs génétiques</term>
<term>Virus du SRAS (génétique)</term>
<term>Virus du SRAS (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en">
<term>Adjuvants, Immunologic</term>
<term>Aluminum Hydroxide</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies, Neutralizing</term>
<term>Antibodies, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr">
<term>Adjuvants immunologiques</term>
<term>Hydroxyde d'aluminium</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Baculoviridae</term>
<term>Membrane Glycoproteins</term>
<term>Recombinant Proteins</term>
<term>SARS Virus</term>
<term>Vaccines, Virosome</term>
<term>Viral Envelope Proteins</term>
<term>Viral Matrix Proteins</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Baculoviridae</term>
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines de la matrice virale</term>
<term>Protéines recombinantes</term>
<term>Vaccins antiviraux</term>
<term>Vaccins à virosomes</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines recombinantes</term>
<term>Vaccins antiviraux</term>
<term>Vaccins à virosomes</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Recombinant Proteins</term>
<term>SARS Virus</term>
<term>Vaccines, Virosome</term>
<term>Viral Envelope Proteins</term>
<term>Viral Vaccines</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Membrane Glycoproteins</term>
<term>Recombinant Proteins</term>
<term>Viral Envelope Proteins</term>
<term>Viral Matrix Proteins</term>
</keywords>
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<term>Glycoprotéines membranaires</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines de la matrice virale</term>
<term>Protéines recombinantes</term>
</keywords>
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<term>Rodent Diseases</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</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>Body Weight</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Genetic Vectors</term>
<term>Insecta</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Protein Multimerization</term>
<term>Spike Glycoprotein, Coronavirus</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>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Maladies des rongeurs</term>
<term>Modèles animaux de maladie humaine</term>
<term>Multimérisation de protéines</term>
<term>Poids du corps</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vecteurs génétiques</term>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.</div>
</front>
</TEI>
</pubmed>
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