Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects
Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. T...
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| description | Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection. |
| doi_str_mv | 10.1371/journal.pntd.0008143 |
| format | Article |
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The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0008143</identifier><identifier>PMID: 32160203</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Neutralizing - administration & dosage ; Antibodies, Viral - administration & dosage ; Antigens, Viral - immunology ; Antiviral agents ; Biology and life sciences ; Coccidioidomycosis ; Disease Models, Animal ; Drug therapy ; Encephalitis ; Epidemics ; Experiments ; Female ; Glycoproteins ; Glycoproteins - immunology ; Health aspects ; Hemorrhage ; Hemorrhagic fever ; Immunization ; Immunoglobulins ; Immunologic Factors - administration & dosage ; Infections ; Infectious diseases ; Laboratories ; Male ; Medicine and health sciences ; Mice, Inbred BALB C ; Monoclonal antibodies ; Mosquitoes ; Neonates ; Neutralization ; Neutralizing ; Physical Sciences ; Physiological aspects ; Proteins ; Research and Analysis Methods ; Rift Valley fever ; Rift Valley Fever - immunology ; Rift Valley Fever - prevention & control ; Rift Valley fever virus - immunology ; RNA polymerase ; Sheep ; Survival ; Survival Analysis ; Therapy ; Treatment Outcome ; Tropical diseases ; Vector-borne diseases ; Veterinary medicine ; Viral diseases ; Viral proteins ; Viruses ; Zoonoses</subject><ispartof>PLoS neglected tropical diseases, 2020-03, Vol.14 (3), p.e0008143-e0008143</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Gutjahr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Gutjahr et al 2020 Gutjahr et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-beabaca6082ef28842c506bca6587c0c6e1bab38940abddf7dc6deda1ecf12bc3</citedby><cites>FETCH-LOGICAL-c624t-beabaca6082ef28842c506bca6587c0c6e1bab38940abddf7dc6deda1ecf12bc3</cites><orcidid>0000-0002-1197-8288 ; 0000-0003-3229-8377</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089562/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089562/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32160203$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bird, Brian</contributor><creatorcontrib>Gutjahr, Benjamin</creatorcontrib><creatorcontrib>Keller, Markus</creatorcontrib><creatorcontrib>Rissmann, Melanie</creatorcontrib><creatorcontrib>von Arnim, Felicitas</creatorcontrib><creatorcontrib>Jäckel, Susanne</creatorcontrib><creatorcontrib>Reiche, Sven</creatorcontrib><creatorcontrib>Ulrich, Reiner</creatorcontrib><creatorcontrib>Groschup, Martin H</creatorcontrib><creatorcontrib>Eiden, Martin</creatorcontrib><title>Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Neutralizing - administration & dosage</subject><subject>Antibodies, Viral - administration & dosage</subject><subject>Antigens, Viral - immunology</subject><subject>Antiviral agents</subject><subject>Biology and life sciences</subject><subject>Coccidioidomycosis</subject><subject>Disease Models, Animal</subject><subject>Drug therapy</subject><subject>Encephalitis</subject><subject>Epidemics</subject><subject>Experiments</subject><subject>Female</subject><subject>Glycoproteins</subject><subject>Glycoproteins - immunology</subject><subject>Health aspects</subject><subject>Hemorrhage</subject><subject>Hemorrhagic fever</subject><subject>Immunization</subject><subject>Immunoglobulins</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medicine and health sciences</subject><subject>Mice, Inbred BALB C</subject><subject>Monoclonal antibodies</subject><subject>Mosquitoes</subject><subject>Neonates</subject><subject>Neutralization</subject><subject>Neutralizing</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Rift Valley fever</subject><subject>Rift Valley Fever - immunology</subject><subject>Rift Valley Fever - prevention & control</subject><subject>Rift Valley fever virus - immunology</subject><subject>RNA polymerase</subject><subject>Sheep</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Therapy</subject><subject>Treatment Outcome</subject><subject>Tropical diseases</subject><subject>Vector-borne diseases</subject><subject>Veterinary medicine</subject><subject>Viral diseases</subject><subject>Viral proteins</subject><subject>Viruses</subject><subject>Zoonoses</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNptkl1rFDEUhgdRbK3-A9GAIN7smo_5vCmUYmuhIEj1NpzJnJlNySRrkl3Zf2-mOy27UnKR5OR535OcnCx7z-iSiYp9vXcbb8Es1zZ2S0ppzXLxIjtljSgWvBLFy4P1SfYmhHtKi6ao2evsRHBWUk7Faba9--vI6KxTxiU3Ajbq1nUaA4EBtA2RDGan3Nq7iNqSa0seliqSUSskvXcj-an7SH6DMbgjV7hFT9Rq2tkBSbsjyrk1eoh6iwT7PmnD2-xVDybgu3k-y35dfbu7_L64_XF9c3lxu1Alz-OiRWhBQUlrjj2v65yrgpZtihR1pagqkbXQirrJKbRd11edKjvsgKHqGW-VOMs-7n3XxgU5lyxILhpasTTqRNzsic7BvVx7PYLfSQdaPgScHyT4qJVBWffQgBJtqSjNecVbKJsau6ZWOYei48nrfM62aUfsFNrowRyZHp9YvZKD28qK1k1RTgZfZgPv_mwwRDnqoNAYsOg2072rshKUijKhn_5Dn3_dTA2QHqBt71JeNZnKi1LwpmCVEIlaPkOl0WH6ZGex1yl-JPh8IFghmLgKzmyidjYcg_keVN6F4LF_Kgajcmrjx1vLqY3l3MZJ9uGwkE-ix74V_wBMzPIm</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Gutjahr, Benjamin</creator><creator>Keller, Markus</creator><creator>Rissmann, Melanie</creator><creator>von Arnim, Felicitas</creator><creator>Jäckel, Susanne</creator><creator>Reiche, Sven</creator><creator>Ulrich, Reiner</creator><creator>Groschup, Martin H</creator><creator>Eiden, Martin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1197-8288</orcidid><orcidid>https://orcid.org/0000-0003-3229-8377</orcidid></search><sort><creationdate>20200301</creationdate><title>Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects</title><author>Gutjahr, Benjamin ; Keller, Markus ; Rissmann, Melanie ; von Arnim, Felicitas ; Jäckel, Susanne ; Reiche, Sven ; Ulrich, Reiner ; Groschup, Martin H ; Eiden, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-beabaca6082ef28842c506bca6587c0c6e1bab38940abddf7dc6deda1ecf12bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal - 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immunology</topic><topic>Rift Valley Fever - prevention & control</topic><topic>Rift Valley fever virus - immunology</topic><topic>RNA polymerase</topic><topic>Sheep</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Therapy</topic><topic>Treatment Outcome</topic><topic>Tropical diseases</topic><topic>Vector-borne diseases</topic><topic>Veterinary medicine</topic><topic>Viral diseases</topic><topic>Viral proteins</topic><topic>Viruses</topic><topic>Zoonoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gutjahr, Benjamin</creatorcontrib><creatorcontrib>Keller, Markus</creatorcontrib><creatorcontrib>Rissmann, Melanie</creatorcontrib><creatorcontrib>von Arnim, Felicitas</creatorcontrib><creatorcontrib>Jäckel, Susanne</creatorcontrib><creatorcontrib>Reiche, Sven</creatorcontrib><creatorcontrib>Ulrich, Reiner</creatorcontrib><creatorcontrib>Groschup, Martin H</creatorcontrib><creatorcontrib>Eiden, Martin</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 & 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 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 & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & 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>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>Gutjahr, Benjamin</au><au>Keller, Markus</au><au>Rissmann, Melanie</au><au>von Arnim, Felicitas</au><au>Jäckel, Susanne</au><au>Reiche, Sven</au><au>Ulrich, Reiner</au><au>Groschup, Martin H</au><au>Eiden, Martin</au><au>Bird, Brian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>14</volume><issue>3</issue><spage>e0008143</spage><epage>e0008143</epage><pages>e0008143-e0008143</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes severe disease in humans and ruminants. The infection is characterized by abortions in pregnant animals, high mortality in neonates as well as febrile illness in humans that develop in 1% of cases encephalitis or hemorrhagic fever. There is presently no specific antiviral treatment for RVFV infection available. In this study, two monoclonal antibodies (mAbs), raised against glycoprotein Gn, were applied in a therapeutic study. Treatment of RVFV infected mice with neutralizing mAb Gn3 alone at two different time points (30 minutes before or 30 minutes after virus challenge) showed only moderate efficacy of about 58.3% survival in both applications. However, a combination therapy together with non-neutralizing mAb Gn32 demonstrated complete protection (100% survival) when applied 30 minutes after the lethal challenge dose. The increase of mAb efficacy is probably based on cooperative neutralization effects. These data suggest that a combination therapy with mAbs Gn3 and Gn32 could be an effective treatment option against RVFV infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32160203</pmid><doi>10.1371/journal.pntd.0008143</doi><orcidid>https://orcid.org/0000-0002-1197-8288</orcidid><orcidid>https://orcid.org/0000-0003-3229-8377</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Antibodies Antibodies, Monoclonal - administration & dosage Antibodies, Neutralizing - administration & dosage Antibodies, Viral - administration & dosage Antigens, Viral - immunology Antiviral agents Biology and life sciences Coccidioidomycosis Disease Models, Animal Drug therapy Encephalitis Epidemics Experiments Female Glycoproteins Glycoproteins - immunology Health aspects Hemorrhage Hemorrhagic fever Immunization Immunoglobulins Immunologic Factors - administration & dosage Infections Infectious diseases Laboratories Male Medicine and health sciences Mice, Inbred BALB C Monoclonal antibodies Mosquitoes Neonates Neutralization Neutralizing Physical Sciences Physiological aspects Proteins Research and Analysis Methods Rift Valley fever Rift Valley Fever - immunology Rift Valley Fever - prevention & control Rift Valley fever virus - immunology RNA polymerase Sheep Survival Survival Analysis Therapy Treatment Outcome Tropical diseases Vector-borne diseases Veterinary medicine Viral diseases Viral proteins Viruses Zoonoses |
| title | Two monoclonal antibodies against glycoprotein Gn protect mice from Rift Valley Fever challenge by cooperative effects |
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