التفاصيل البيبلوغرافية
| العنوان: |
Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2. |
| المؤلفون: |
Feng Y, Yuan M, Powers JM, Hu M, Munt JE, Arunachalam PS, Leist SR, Bellusci L, Adams LE, Sundaramurthy S, Shirreff LM, Mallory ML, Scooby TD, Moreno A, O'Hagan DT, Kleanthous H, Villinger FJ, Veesler D, King NP, Suthar MS, Khurana S, Baric RS, Wilson IA, Pulendran B |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Jan 20. Date of Electronic Publication: 2023 Jan 20. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (∼4.4%) antibodies isolated at 1.4∼6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies.
One Sentence Summary: Extremely potent pan-sarbecovirus neutralizing antibodies. |
| معلومات مُعتمدة: |
U19 AI167903 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230130 Latest Revision: 20231208 |
| رمز التحديث: |
20231215 |
| مُعرف محوري في PubMed: |
PMC9882348 |
| DOI: |
10.1101/2023.01.19.524784 |
| PMID: |
36711543 |
| قاعدة البيانات: |
MEDLINE |
