Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012456 |
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| author | Christopher T Edwards Kirti A Karunakaran Elijah Garcia Nathan Beutler Matthew Gagne Nadia Golden Hadj Aoued Kathryn L Pellegrini Matthew R Burnett Christopher Cole Honeycutt Stacey A Lapp Thang Ton Mark C Lin Amanda Metz Andrei Bombin Kelly Goff Sarah E Scheuermann Amelia Wilkes Jennifer S Wood Stephanie Ehnert Stacey Weissman Elizabeth H Curran Melissa Roy Evan Dessasau Mirko Paiardini Amit A Upadhyay Ian N Moore Nicholas J Maness Daniel C Douek Anne Piantadosi Raiees Andrabi Thomas R Rogers Dennis R Burton Steven E Bosinger |
| author_facet | Christopher T Edwards Kirti A Karunakaran Elijah Garcia Nathan Beutler Matthew Gagne Nadia Golden Hadj Aoued Kathryn L Pellegrini Matthew R Burnett Christopher Cole Honeycutt Stacey A Lapp Thang Ton Mark C Lin Amanda Metz Andrei Bombin Kelly Goff Sarah E Scheuermann Amelia Wilkes Jennifer S Wood Stephanie Ehnert Stacey Weissman Elizabeth H Curran Melissa Roy Evan Dessasau Mirko Paiardini Amit A Upadhyay Ian N Moore Nicholas J Maness Daniel C Douek Anne Piantadosi Raiees Andrabi Thomas R Rogers Dennis R Burton Steven E Bosinger |
| author_sort | Christopher T Edwards |
| collection | DOAJ |
| description | The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines. |
| format | Article |
| id | doaj-art-7092eeafc6b04a23ada73b733188590b |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-7092eeafc6b04a23ada73b733188590b2025-02-08T05:30:30ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101245610.1371/journal.ppat.1012456Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.Christopher T EdwardsKirti A KarunakaranElijah GarciaNathan BeutlerMatthew GagneNadia GoldenHadj AouedKathryn L PellegriniMatthew R BurnettChristopher Cole HoneycuttStacey A LappThang TonMark C LinAmanda MetzAndrei BombinKelly GoffSarah E ScheuermannAmelia WilkesJennifer S WoodStephanie EhnertStacey WeissmanElizabeth H CurranMelissa RoyEvan DessasauMirko PaiardiniAmit A UpadhyayIan N MooreNicholas J ManessDaniel C DouekAnne PiantadosiRaiees AndrabiThomas R RogersDennis R BurtonSteven E BosingerThe continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.https://doi.org/10.1371/journal.ppat.1012456 |
| spellingShingle | Christopher T Edwards Kirti A Karunakaran Elijah Garcia Nathan Beutler Matthew Gagne Nadia Golden Hadj Aoued Kathryn L Pellegrini Matthew R Burnett Christopher Cole Honeycutt Stacey A Lapp Thang Ton Mark C Lin Amanda Metz Andrei Bombin Kelly Goff Sarah E Scheuermann Amelia Wilkes Jennifer S Wood Stephanie Ehnert Stacey Weissman Elizabeth H Curran Melissa Roy Evan Dessasau Mirko Paiardini Amit A Upadhyay Ian N Moore Nicholas J Maness Daniel C Douek Anne Piantadosi Raiees Andrabi Thomas R Rogers Dennis R Burton Steven E Bosinger Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. PLoS Pathogens |
| title | Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. |
| title_full | Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. |
| title_fullStr | Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. |
| title_full_unstemmed | Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. |
| title_short | Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques. |
| title_sort | passive infusion of an s2 stem broadly neutralizing antibody protects against sars cov 2 infection and lower airway inflammation in rhesus macaques |
| url | https://doi.org/10.1371/journal.ppat.1012456 |
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