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TitleIdentification and Analysis of Monoclonal Antibodies with Neutralizing Activity against Diverse SARS-CoV-2 Variants.
Journal, issue, pagesJ Virol, Vol. 97, Issue 6, Page e0028623, Year 2023
Publish dateJun 29, 2023
AuthorsHanako Ishimaru / Mitsuhiro Nishimura / Lidya Handayani Tjan / Silvia Sutandhio / Maria Istiqomah Marini / Gema Barlian Effendi / Hideki Shigematsu / Koji Kato / Natsumi Hasegawa / Kaito Aoki / Yukiya Kurahashi / Koichi Furukawa / Mai Shinohara / Tomoka Nakamura / Jun Arii / Tatsuya Nagano / Sachiko Nakamura / Shigeru Sano / Sachiyo Iwata / Shinya Okamura / Yasuko Mori /
PubMed AbstractWe 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 ...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. 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.
External linksJ Virol / PubMed:37191569 / PubMed Central
MethodsEM (single particle)
Resolution2.48 - 3.85 Å
Structure data

34469

8h3m

EMDB-34469, PDB-8h3m:
Conformation 1 of SARS-CoV-2 Omicron BA.1 Variant Spike protein complexed with MO1 Fab
Method: EM (single particle) / Resolution: 2.48 Å

34470

8h3n

EMDB-34470, PDB-8h3n:
Conformation 2 of SARS-CoV-2 Omicron BA.1 Variant Spike protein complexed with MO1 Fab
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-34488: Conformation 3 of SARS-CoV-2 Omicron BA.1 Variant Spike protein complexed with MO1 Fab
Method: EM (single particle) / Resolution: 3.85 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2

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