Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen
Identifieur interne : 001A63 ( Main/Exploration ); précédent : 001A62; suivant : 001A64Tailoring Subunit Vaccine Immunity with Adjuvant Combinations and Delivery Routes Using the Middle East Respiratory Coronavirus (MERS-CoV) Receptor-Binding Domain as an Antigen
Auteurs : Jiaming Lan [République populaire de Chine] ; Yao Deng [République populaire de Chine] ; Hong Chen [République populaire de Chine] ; Guangwen Lu [République populaire de Chine] ; Wen Wang [République populaire de Chine] ; Xiaojuan Guo [République populaire de Chine] ; Zhuozhuang Lu [République populaire de Chine] ; George F. Gao [République populaire de Chine] ; Wenjie Tan [République populaire de Chine]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Descripteurs français
- KwdFr :
- Adjuvants immunologiques (administration et posologie), Animaux, Antigènes viraux (immunologie), Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie), Immunisation (), Immunité cellulaire, Immunité humorale, Souris, Souris de lignée BALB C, Systèmes de délivrance de médicaments (), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie).
- MESH :
- administration et posologie : Adjuvants immunologiques, Vaccins antiviraux.
- immunologie : Antigènes viraux, Coronavirus du syndrome respiratoire du Moyen-Orient, Vaccins antiviraux.
- Animaux, Coronavirus du syndrome respiratoire du Moyen-Orient, Immunisation, Immunité cellulaire, Immunité humorale, Souris, Souris de lignée BALB C, Systèmes de délivrance de médicaments.
English descriptors
- KwdEn :
- Adjuvants, Immunologic (administration & dosage), Animals, Antigens, Viral (immunology), Drug Delivery Systems (methods), Immunity, Cellular, Immunity, Humoral, Immunization (methods), Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (immunology), Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Adjuvants, Immunologic, Viral Vaccines.
- chemical , immunology : Antigens, Viral, Viral Vaccines.
- chemistry : Middle East Respiratory Syndrome Coronavirus.
- immunology : Middle East Respiratory Syndrome Coronavirus.
- methods : Drug Delivery Systems, Immunization.
- Animals, Immunity, Cellular, Immunity, Humoral, Mice, Mice, Inbred BALB C.
Abstract
The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.
Url:
DOI: 10.1371/journal.pone.0112602
PubMed: 25405618
PubMed Central: 4236105
Affiliations:
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Guo</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lu, Zhuozhuang" sort="Lu, Zhuozhuang" uniqKey="Lu Z" first="Zhuozhuang" last="Lu">Zhuozhuang Lu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China</addr-line></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adjuvants, Immunologic (administration & dosage)</term><term>Animals</term><term>Antigens, Viral (immunology)</term><term>Drug Delivery Systems (methods)</term><term>Immunity, Cellular</term><term>Immunity, Humoral</term><term>Immunization (methods)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term><term>Middle East Respiratory Syndrome Coronavirus (immunology)</term><term>Viral Vaccines (administration & dosage)</term><term>Viral Vaccines (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adjuvants immunologiques (administration et posologie)</term><term>Animaux</term><term>Antigènes viraux (immunologie)</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (immunologie)</term><term>Immunisation ()</term><term>Immunité cellulaire</term><term>Immunité humorale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Systèmes de délivrance de médicaments ()</term><term>Vaccins antiviraux (administration et posologie)</term><term>Vaccins antiviraux (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adjuvants, Immunologic</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antigens, Viral</term><term>Viral Vaccines</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Adjuvants immunologiques</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Vaccins antiviraux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Delivery Systems</term><term>Immunization</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Immunity, Cellular</term><term>Immunity, Humoral</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Immunisation</term><term>Immunité cellulaire</term><term>Immunité humorale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Systèmes de délivrance de médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, L" uniqKey="Lu L">L Lu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S 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first="Yao" last="Deng">Yao Deng</name><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name><name sortKey="Guo, Xiaojuan" sort="Guo, Xiaojuan" uniqKey="Guo X" first="Xiaojuan" last="Guo">Xiaojuan Guo</name><name sortKey="Lan, Jiaming" sort="Lan, Jiaming" uniqKey="Lan J" first="Jiaming" last="Lan">Jiaming Lan</name><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><name sortKey="Lu, Zhuozhuang" sort="Lu, Zhuozhuang" uniqKey="Lu Z" first="Zhuozhuang" last="Lu">Zhuozhuang Lu</name><name sortKey="Tan, Wenjie" sort="Tan, Wenjie" uniqKey="Tan W" first="Wenjie" last="Tan">Wenjie Tan</name><name sortKey="Wang, Wen" sort="Wang, Wen" uniqKey="Wang W" first="Wen" last="Wang">Wen Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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