Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples

Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased...

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Veröffentlicht in:PLoS neglected tropical diseases 2020-10, Vol.14 (10), p.e0008699-e0008699
Hauptverfasser: Surtees, Rebecca, Stern, Daniel, Ahrens, Katharina, Kromarek, Nicole, Lander, Angelika, Kreher, Petra, Weiss, Sabrina, Hewson, Roger, Punch, Emma K, Barr, John N, Witkowski, Peter T, Couacy-Hymann, Emmanuel, Marzi, Andrea, Dorner, Brigitte G, Kurth, Andreas
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container_issue 10
container_start_page e0008699
container_title PLoS neglected tropical diseases
container_volume 14
creator Surtees, Rebecca
Stern, Daniel
Ahrens, Katharina
Kromarek, Nicole
Lander, Angelika
Kreher, Petra
Weiss, Sabrina
Hewson, Roger
Punch, Emma K
Barr, John N
Witkowski, Peter T
Couacy-Hymann, Emmanuel
Marzi, Andrea
Dorner, Brigitte G
Kurth, Andreas
description Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses.
doi_str_mv 10.1371/journal.pntd.0008699
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Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. 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blood</topic><topic>Antigens</topic><topic>Binding</topic><topic>Biology and life sciences</topic><topic>Cellular biology</topic><topic>Chiroptera</topic><topic>Coccidioidomycosis</topic><topic>Crimean hemorrhagic fever</topic><topic>Defence mechanisms</topic><topic>Detection</topic><topic>Diagnosis</topic><topic>Disease</topic><topic>Early warning systems</topic><topic>Ebola virus</topic><topic>ELISA</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epidemics</topic><topic>Filoviridae</topic><topic>Funding</topic><topic>Hantavirus</topic><topic>Health aspects</topic><topic>Health surveillance</topic><topic>High-throughput screening (Biochemical assaying)</topic><topic>Human populations</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunoassay</topic><topic>Immunoassay - methods</topic><topic>Immunoassays</topic><topic>Immunoglobulin G</topic><topic>Infections</topic><topic>Inoculation</topic><topic>Laboratories</topic><topic>Livestock</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Microspheres</topic><topic>Monitoring</topic><topic>Multiplexing</topic><topic>Nosocomial infections</topic><topic>Nucleocapsid Proteins - immunology</topic><topic>Nucleocapsids</topic><topic>Nucleoproteins</topic><topic>Optimization</topic><topic>Orthohantavirus</topic><topic>Outbreaks</topic><topic>Pathogens</topic><topic>Populations</topic><topic>Primates</topic><topic>Proteins</topic><topic>Public health</topic><topic>Research and Analysis Methods</topic><topic>Rift Valley fever</topic><topic>Samples</topic><topic>Serology</topic><topic>Serum</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Stern, Daniel</topic><topic>Tropical diseases</topic><topic>Vector-borne diseases</topic><topic>Viral antibodies</topic><topic>Viral diseases</topic><topic>Virology</topic><topic>Virus diseases</topic><topic>Virus Diseases - diagnosis</topic><topic>Virus Diseases - veterinary</topic><topic>Virus Diseases - virology</topic><topic>Virus-like particles</topic><topic>Viruses</topic><topic>Wildlife</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Surtees, Rebecca</creatorcontrib><creatorcontrib>Stern, Daniel</creatorcontrib><creatorcontrib>Ahrens, Katharina</creatorcontrib><creatorcontrib>Kromarek, Nicole</creatorcontrib><creatorcontrib>Lander, Angelika</creatorcontrib><creatorcontrib>Kreher, Petra</creatorcontrib><creatorcontrib>Weiss, Sabrina</creatorcontrib><creatorcontrib>Hewson, Roger</creatorcontrib><creatorcontrib>Punch, Emma K</creatorcontrib><creatorcontrib>Barr, John N</creatorcontrib><creatorcontrib>Witkowski, Peter T</creatorcontrib><creatorcontrib>Couacy-Hymann, Emmanuel</creatorcontrib><creatorcontrib>Marzi, Andrea</creatorcontrib><creatorcontrib>Dorner, Brigitte G</creatorcontrib><creatorcontrib>Kurth, Andreas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 1: Biological Sciences &amp; Living Resources</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 3: Aquatic Pollution &amp; Environmental Quality</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Professional</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Surtees, Rebecca</au><au>Stern, Daniel</au><au>Ahrens, Katharina</au><au>Kromarek, Nicole</au><au>Lander, Angelika</au><au>Kreher, Petra</au><au>Weiss, Sabrina</au><au>Hewson, Roger</au><au>Punch, Emma K</au><au>Barr, John N</au><au>Witkowski, Peter T</au><au>Couacy-Hymann, Emmanuel</au><au>Marzi, Andrea</au><au>Dorner, Brigitte G</au><au>Kurth, Andreas</au><au>McElroy, Anita K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>14</volume><issue>10</issue><spage>e0008699</spage><epage>e0008699</epage><pages>e0008699-e0008699</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33095766</pmid><doi>10.1371/journal.pntd.0008699</doi><orcidid>https://orcid.org/0000-0002-4835-3695</orcidid><orcidid>https://orcid.org/0000-0003-0186-9587</orcidid><orcidid>https://orcid.org/0000-0003-0265-8407</orcidid><orcidid>https://orcid.org/0000-0001-9057-4283</orcidid><orcidid>https://orcid.org/0000-0002-5100-2546</orcidid><orcidid>https://orcid.org/0000-0002-6167-8945</orcidid><orcidid>https://orcid.org/0000-0002-9035-2039</orcidid><orcidid>https://orcid.org/0000-0002-5477-6619</orcidid><orcidid>https://orcid.org/0000-0002-6621-6379</orcidid><orcidid>https://orcid.org/0000-0002-9660-9878</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1935-2735
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issn 1935-2735
1935-2727
1935-2735
language eng
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS); PubMed Central
subjects Animal population
Animal populations
Animals
Antibodies
Antibodies, Viral - blood
Antigens
Binding
Biology and life sciences
Cellular biology
Chiroptera
Coccidioidomycosis
Crimean hemorrhagic fever
Defence mechanisms
Detection
Diagnosis
Disease
Early warning systems
Ebola virus
ELISA
Enzyme-linked immunosorbent assay
Epidemics
Filoviridae
Funding
Hantavirus
Health aspects
Health surveillance
High-throughput screening (Biochemical assaying)
Human populations
Humans
Immune response
Immune system
Immunity
Immunoassay
Immunoassay - methods
Immunoassays
Immunoglobulin G
Infections
Inoculation
Laboratories
Livestock
Medicine and Health Sciences
Methods
Microspheres
Monitoring
Multiplexing
Nosocomial infections
Nucleocapsid Proteins - immunology
Nucleocapsids
Nucleoproteins
Optimization
Orthohantavirus
Outbreaks
Pathogens
Populations
Primates
Proteins
Public health
Research and Analysis Methods
Rift Valley fever
Samples
Serology
Serum
Statistical analysis
Statistical methods
Stern, Daniel
Tropical diseases
Vector-borne diseases
Viral antibodies
Viral diseases
Virology
Virus diseases
Virus Diseases - diagnosis
Virus Diseases - veterinary
Virus Diseases - virology
Virus-like particles
Viruses
Wildlife
Zoonoses
title Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples
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