Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants
We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
|---|---|
| Enthalten in: |
Journal of virology - 97(2023), 6 vom: 29. Juni, Seite e0028623 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ishimaru, Hanako [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 18.07.2023 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1128/jvi.00286-23 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356942112 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356942112 | ||
| 003 | DE-627 | ||
| 005 | 20231227131249.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1128/jvi.00286-23 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1225.xml |
| 035 | |a (DE-627)NLM356942112 | ||
| 035 | |a (NLM)37191569 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ishimaru, Hanako |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.07.2023 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Omicron variants | |
| 650 | 4 | |a broad neutralizing activity | |
| 650 | 4 | |a common epitope | |
| 650 | 4 | |a cryoelectron microscopy | |
| 650 | 4 | |a human monoclonal antibody | |
| 650 | 4 | |a receptor-binding domain | |
| 650 | 4 | |a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) | |
| 650 | 4 | |a spike | |
| 650 | 4 | |a vaccine | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Nishimura, Mitsuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Tjan, Lidya Handayani |e verfasserin |4 aut | |
| 700 | 1 | |a Sutandhio, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Marini, Maria Istiqomah |e verfasserin |4 aut | |
| 700 | 1 | |a Effendi, Gema Barlian |e verfasserin |4 aut | |
| 700 | 1 | |a Shigematsu, Hideki |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Hasegawa, Natsumi |e verfasserin |4 aut | |
| 700 | 1 | |a Aoki, Kaito |e verfasserin |4 aut | |
| 700 | 1 | |a Kurahashi, Yukiya |e verfasserin |4 aut | |
| 700 | 1 | |a Furukawa, Koichi |e verfasserin |4 aut | |
| 700 | 1 | |a Shinohara, Mai |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Tomoka |e verfasserin |4 aut | |
| 700 | 1 | |a Arii, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Nagano, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Sachiko |e verfasserin |4 aut | |
| 700 | 1 | |a Sano, Shigeru |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Sachiyo |e verfasserin |4 aut | |
| 700 | 1 | |a Okamura, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Mori, Yasuko |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of virology |d 1967 |g 97(2023), 6 vom: 29. Juni, Seite e0028623 |w (DE-627)NLM000006866 |x 1098-5514 |7 nnns |
| 773 | 1 | 8 | |g volume:97 |g year:2023 |g number:6 |g day:29 |g month:06 |g pages:e0028623 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1128/jvi.00286-23 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 97 |j 2023 |e 6 |b 29 |c 06 |h e0028623 | ||