Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice

Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vacc...

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Veröffentlicht in:Antiviral research 2017-04, Vol.140, p.55-61
Hauptverfasser: Wang, Chong, Zheng, Xuexing, Gai, Weiwei, Wong, Gary, Wang, Hualei, Jin, Hongli, Feng, Na, Zhao, Yongkun, Zhang, Weijiao, Li, Nan, Zhao, Guoxing, Li, Junfu, Yan, Jinghua, Gao, Yuwei, Hu, Guixue, Yang, Songtao, Xia, Xianzhu
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container_issue
container_start_page 55
container_title Antiviral research
container_volume 140
creator Wang, Chong
Zheng, Xuexing
Gai, Weiwei
Wong, Gary
Wang, Hualei
Jin, Hongli
Feng, Na
Zhao, Yongkun
Zhang, Weijiao
Li, Nan
Zhao, Guoxing
Li, Junfu
Yan, Jinghua
Gao, Yuwei
Hu, Guixue
Yang, Songtao
Xia, Xianzhu
description Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation. •We constructed a chimeric parvovirus virus-like particles displaying the MERS-CoV receptor-binding domain on the surface.•We found that the chimeric virus-like particles induced RBD-specific, neutralizing antibody responses in mice.•Splenocytes from immunized mice had considerably higher secretion of both Th1- and Th2-type cytokines.•Our results reveal that chimeric virus-like particles induce both specific humoral and cell-mediated immunity.
doi_str_mv 10.1016/j.antiviral.2016.12.019
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Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation. •We constructed a chimeric parvovirus virus-like particles displaying the MERS-CoV receptor-binding domain on the surface.•We found that the chimeric virus-like particles induced RBD-specific, neutralizing antibody responses in mice.•Splenocytes from immunized mice had considerably higher secretion of both Th1- and Th2-type cytokines.•Our results reveal that chimeric virus-like particles induce both specific humoral and cell-mediated immunity.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/j.antiviral.2016.12.019</identifier><identifier>PMID: 28040513</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adjuvants, Immunologic ; Animals ; Antibodies, Neutralizing - blood ; Antibodies, Viral - blood ; Capsid Proteins - genetics ; Capsid Proteins - immunology ; Chimera ; Coronavirus Infections - prevention &amp; control ; CPV ; Cytokines - immunology ; Cytokines - metabolism ; Erythrocytes - virology ; Immune response ; Immunity, Cellular ; Immunity, Humoral ; Mice ; Middle East respiratory syndrome coronavirus ; Middle East Respiratory Syndrome Coronavirus - genetics ; Parvovirus, Canine - genetics ; Protein Binding ; Receptor binding domain ; Swine ; Th1 Cells - immunology ; Th2 Cells - immunology ; Vaccines, Virus-Like Particle - genetics ; Vaccines, Virus-Like Particle - immunology ; Viral Vaccines - administration &amp; dosage ; Viral Vaccines - immunology ; Virus-like particles</subject><ispartof>Antiviral research, 2017-04, Vol.140, p.55-61</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><rights>2017 Elsevier B.V. All rights reserved. 2017 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-288ac8f688022f606eb327de59af60951c06c4c0307c33e9902d5169088b955f3</citedby><cites>FETCH-LOGICAL-c475t-288ac8f688022f606eb327de59af60951c06c4c0307c33e9902d5169088b955f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.antiviral.2016.12.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28040513$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Chong</creatorcontrib><creatorcontrib>Zheng, Xuexing</creatorcontrib><creatorcontrib>Gai, Weiwei</creatorcontrib><creatorcontrib>Wong, Gary</creatorcontrib><creatorcontrib>Wang, Hualei</creatorcontrib><creatorcontrib>Jin, Hongli</creatorcontrib><creatorcontrib>Feng, Na</creatorcontrib><creatorcontrib>Zhao, Yongkun</creatorcontrib><creatorcontrib>Zhang, Weijiao</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Zhao, Guoxing</creatorcontrib><creatorcontrib>Li, Junfu</creatorcontrib><creatorcontrib>Yan, Jinghua</creatorcontrib><creatorcontrib>Gao, Yuwei</creatorcontrib><creatorcontrib>Hu, Guixue</creatorcontrib><creatorcontrib>Yang, Songtao</creatorcontrib><creatorcontrib>Xia, Xianzhu</creatorcontrib><title>Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice</title><title>Antiviral research</title><addtitle>Antiviral Res</addtitle><description>Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation. •We constructed a chimeric parvovirus virus-like particles displaying the MERS-CoV receptor-binding domain on the surface.•We found that the chimeric virus-like particles induced RBD-specific, neutralizing antibody responses in mice.•Splenocytes from immunized mice had considerably higher secretion of both Th1- and Th2-type cytokines.•Our results reveal that chimeric virus-like particles induce both specific humoral and cell-mediated immunity.</description><subject>Adjuvants, Immunologic</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Viral - blood</subject><subject>Capsid Proteins - genetics</subject><subject>Capsid Proteins - immunology</subject><subject>Chimera</subject><subject>Coronavirus Infections - prevention &amp; control</subject><subject>CPV</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>Erythrocytes - virology</subject><subject>Immune response</subject><subject>Immunity, Cellular</subject><subject>Immunity, Humoral</subject><subject>Mice</subject><subject>Middle East respiratory syndrome coronavirus</subject><subject>Middle East Respiratory Syndrome Coronavirus - genetics</subject><subject>Parvovirus, Canine - genetics</subject><subject>Protein Binding</subject><subject>Receptor binding domain</subject><subject>Swine</subject><subject>Th1 Cells - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Vaccines, Virus-Like Particle - genetics</subject><subject>Vaccines, Virus-Like Particle - immunology</subject><subject>Viral Vaccines - administration &amp; 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Zheng, Xuexing ; Gai, Weiwei ; Wong, Gary ; Wang, Hualei ; Jin, Hongli ; Feng, Na ; Zhao, Yongkun ; Zhang, Weijiao ; Li, Nan ; Zhao, Guoxing ; Li, Junfu ; Yan, Jinghua ; Gao, Yuwei ; Hu, Guixue ; Yang, Songtao ; Xia, Xianzhu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-288ac8f688022f606eb327de59af60951c06c4c0307c33e9902d5169088b955f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adjuvants, Immunologic</topic><topic>Animals</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Viral - blood</topic><topic>Capsid Proteins - genetics</topic><topic>Capsid Proteins - immunology</topic><topic>Chimera</topic><topic>Coronavirus Infections - prevention &amp; control</topic><topic>CPV</topic><topic>Cytokines - immunology</topic><topic>Cytokines - metabolism</topic><topic>Erythrocytes - virology</topic><topic>Immune response</topic><topic>Immunity, Cellular</topic><topic>Immunity, Humoral</topic><topic>Mice</topic><topic>Middle East respiratory syndrome coronavirus</topic><topic>Middle East Respiratory Syndrome Coronavirus - genetics</topic><topic>Parvovirus, Canine - genetics</topic><topic>Protein Binding</topic><topic>Receptor binding domain</topic><topic>Swine</topic><topic>Th1 Cells - immunology</topic><topic>Th2 Cells - immunology</topic><topic>Vaccines, Virus-Like Particle - genetics</topic><topic>Vaccines, Virus-Like Particle - immunology</topic><topic>Viral Vaccines - administration &amp; dosage</topic><topic>Viral Vaccines - immunology</topic><topic>Virus-like particles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Chong</creatorcontrib><creatorcontrib>Zheng, Xuexing</creatorcontrib><creatorcontrib>Gai, Weiwei</creatorcontrib><creatorcontrib>Wong, Gary</creatorcontrib><creatorcontrib>Wang, Hualei</creatorcontrib><creatorcontrib>Jin, Hongli</creatorcontrib><creatorcontrib>Feng, Na</creatorcontrib><creatorcontrib>Zhao, Yongkun</creatorcontrib><creatorcontrib>Zhang, Weijiao</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Zhao, Guoxing</creatorcontrib><creatorcontrib>Li, Junfu</creatorcontrib><creatorcontrib>Yan, Jinghua</creatorcontrib><creatorcontrib>Gao, Yuwei</creatorcontrib><creatorcontrib>Hu, Guixue</creatorcontrib><creatorcontrib>Yang, Songtao</creatorcontrib><creatorcontrib>Xia, Xianzhu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antiviral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Chong</au><au>Zheng, Xuexing</au><au>Gai, Weiwei</au><au>Wong, Gary</au><au>Wang, Hualei</au><au>Jin, Hongli</au><au>Feng, Na</au><au>Zhao, Yongkun</au><au>Zhang, Weijiao</au><au>Li, Nan</au><au>Zhao, Guoxing</au><au>Li, Junfu</au><au>Yan, Jinghua</au><au>Gao, Yuwei</au><au>Hu, Guixue</au><au>Yang, Songtao</au><au>Xia, Xianzhu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice</atitle><jtitle>Antiviral research</jtitle><addtitle>Antiviral Res</addtitle><date>2017-04-01</date><risdate>2017</risdate><volume>140</volume><spage>55</spage><epage>61</epage><pages>55-61</pages><issn>0166-3542</issn><eissn>1872-9096</eissn><abstract>Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. 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subjects Adjuvants, Immunologic
Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Capsid Proteins - genetics
Capsid Proteins - immunology
Chimera
Coronavirus Infections - prevention & control
CPV
Cytokines - immunology
Cytokines - metabolism
Erythrocytes - virology
Immune response
Immunity, Cellular
Immunity, Humoral
Mice
Middle East respiratory syndrome coronavirus
Middle East Respiratory Syndrome Coronavirus - genetics
Parvovirus, Canine - genetics
Protein Binding
Receptor binding domain
Swine
Th1 Cells - immunology
Th2 Cells - immunology
Vaccines, Virus-Like Particle - genetics
Vaccines, Virus-Like Particle - immunology
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
Virus-like particles
title Novel chimeric virus-like particles vaccine displaying MERS-CoV receptor-binding domain induce specific humoral and cellular immune response in mice
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