A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus
The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2018
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| _version_ | 1826302725792464896 |
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| author | Allen, ER Krumm, SA Raghwani, J Halldorsson, S Elliott, A Graham, VA Koudriakova, E Harlos, K Wright, D Warimwe, GM Brennan, B Huiskonen, JT Dowall, SD Elliott, RM Pybus, OG Burton, DR Hewson, R Doores, KJ Bowden, TA |
| author_facet | Allen, ER Krumm, SA Raghwani, J Halldorsson, S Elliott, A Graham, VA Koudriakova, E Harlos, K Wright, D Warimwe, GM Brennan, B Huiskonen, JT Dowall, SD Elliott, RM Pybus, OG Burton, DR Hewson, R Doores, KJ Bowden, TA |
| author_sort | Allen, ER |
| collection | OXFORD |
| description | The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally. |
| first_indexed | 2024-03-07T05:51:55Z |
| format | Journal article |
| id | oxford-uuid:e92e894b-4bf5-4b11-91d0-ad85c0658ae1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:51:55Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:e92e894b-4bf5-4b11-91d0-ad85c0658ae12022-03-27T10:52:30ZA protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e92e894b-4bf5-4b11-91d0-ad85c0658ae1EnglishSymplectic Elements at OxfordElsevier2018Allen, ERKrumm, SARaghwani, JHalldorsson, SElliott, AGraham, VAKoudriakova, EHarlos, KWright, DWarimwe, GMBrennan, BHuiskonen, JTDowall, SDElliott, RMPybus, OGBurton, DRHewson, RDoores, KJBowden, TAThe Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally. |
| spellingShingle | Allen, ER Krumm, SA Raghwani, J Halldorsson, S Elliott, A Graham, VA Koudriakova, E Harlos, K Wright, D Warimwe, GM Brennan, B Huiskonen, JT Dowall, SD Elliott, RM Pybus, OG Burton, DR Hewson, R Doores, KJ Bowden, TA A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title | A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title_full | A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title_fullStr | A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title_full_unstemmed | A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title_short | A protective monoclonal antibody targets a site of vulnerability on the surface of Rift Valley fever virus |
| title_sort | protective monoclonal antibody targets a site of vulnerability on the surface of rift valley fever virus |
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