tetano
Editor, Senior Moderator
Antiviral Res
. 2022 Mar 24;105297.
doi: 10.1016/j.antiviral.2022.105297. Online ahead of print.
Isolation of human monoclonal antibodies with neutralizing activity to a broad spectrum of SARS-CoV-2 viruses including the Omicron variants
Mikako Ueno[SUP] 1 [/SUP], Naoko Iwata-Yoshikawa[SUP] 2 [/SUP], Akihito Matsunaga[SUP] 1 [/SUP], Tadashi Okamura[SUP] 3 [/SUP], Sho Saito[SUP] 4 [/SUP], Shinobu Ashida[SUP] 4 [/SUP], Isao Yoshida[SUP] 5 [/SUP], Mami Nagashima[SUP] 5 [/SUP], Hiroyuki Asakura[SUP] 5 [/SUP], Yuu I Yaoita[SUP] 5 [/SUP], Jun Suzuki[SUP] 5 [/SUP], Kenji Sadamasu[SUP] 5 [/SUP], Kazuhisa Yoshimura[SUP] 5 [/SUP], Satoshi Kutsuna[SUP] 6 [/SUP], Nozomi Shiwa-Sudo[SUP] 2 [/SUP], Noriyo Nagata[SUP] 2 [/SUP], Tadaki Suzuki[SUP] 2 [/SUP], Akinori Suzuki[SUP] 7 [/SUP], Miwa Okamoto[SUP] 7 [/SUP], Moto Kimura[SUP] 8 [/SUP], Norio Ohmagari[SUP] 4 [/SUP], Ryu Miura[SUP] 9 [/SUP], Yukihito Ishizaka[SUP] 10 [/SUP]
Affiliations
Abstract
Monoclonal antibody therapy is a promising option for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a cocktail of antibodies (REGN-COV) has been administered to infected patients with a favorable outcome. However, it is necessary to continue generating novel sets of monoclonal antibodies with neutralizing activity because viral variants can emerge that show resistance to the currently utilized antibodies. Here, we isolated a new cocktail of antibodies, EV053273 and EV053286, from peripheral blood mononuclear cells derived from convalescent patients infected with wild-type SARS-CoV-2. EV053273 exerted potent antiviral activity against the Wunan wild-type virus as well as the Alpha and Delta variants in vitro, whereas the antiviral activity of EV053286 was moderate, but it had a wide-range of suppressive activity on the wild-type virus as well as the Alpha, Beta, Delta, Kappa, Omicron BA.1, and BA.2 variants. With the combined use of EV053273 and EV053286, we observed similar inhibitory effects on viral replication as with REGN-COV in vitro. We further assessed their activity in vivo by using a mouse model infected with a recently established viral strain with adopted infectious activity in mice. Independent experiments revealed that the combined use of EV053273 and EV053286 or the single use of each monoclonal antibody efficiently blocked infection in vivo. Together with data showing that these two monoclonal antibodies could neutralize REGN-COV escape variants and the Omicron variant, our findings suggest that the EV053273 and EV053286 monoclonal antibody cocktail is a novel clinically applicable therapeutic candidate for SARS-CoV-2 infection.
Keywords: Escape mutants; Neutralizing activity; Omicron variants; SARS-CoV-2; Spike protein; mAb.
. 2022 Mar 24;105297.
doi: 10.1016/j.antiviral.2022.105297. Online ahead of print.
Isolation of human monoclonal antibodies with neutralizing activity to a broad spectrum of SARS-CoV-2 viruses including the Omicron variants
Mikako Ueno[SUP] 1 [/SUP], Naoko Iwata-Yoshikawa[SUP] 2 [/SUP], Akihito Matsunaga[SUP] 1 [/SUP], Tadashi Okamura[SUP] 3 [/SUP], Sho Saito[SUP] 4 [/SUP], Shinobu Ashida[SUP] 4 [/SUP], Isao Yoshida[SUP] 5 [/SUP], Mami Nagashima[SUP] 5 [/SUP], Hiroyuki Asakura[SUP] 5 [/SUP], Yuu I Yaoita[SUP] 5 [/SUP], Jun Suzuki[SUP] 5 [/SUP], Kenji Sadamasu[SUP] 5 [/SUP], Kazuhisa Yoshimura[SUP] 5 [/SUP], Satoshi Kutsuna[SUP] 6 [/SUP], Nozomi Shiwa-Sudo[SUP] 2 [/SUP], Noriyo Nagata[SUP] 2 [/SUP], Tadaki Suzuki[SUP] 2 [/SUP], Akinori Suzuki[SUP] 7 [/SUP], Miwa Okamoto[SUP] 7 [/SUP], Moto Kimura[SUP] 8 [/SUP], Norio Ohmagari[SUP] 4 [/SUP], Ryu Miura[SUP] 9 [/SUP], Yukihito Ishizaka[SUP] 10 [/SUP]
Affiliations
- PMID: 35341809
- DOI: 10.1016/j.antiviral.2022.105297
Abstract
Monoclonal antibody therapy is a promising option for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a cocktail of antibodies (REGN-COV) has been administered to infected patients with a favorable outcome. However, it is necessary to continue generating novel sets of monoclonal antibodies with neutralizing activity because viral variants can emerge that show resistance to the currently utilized antibodies. Here, we isolated a new cocktail of antibodies, EV053273 and EV053286, from peripheral blood mononuclear cells derived from convalescent patients infected with wild-type SARS-CoV-2. EV053273 exerted potent antiviral activity against the Wunan wild-type virus as well as the Alpha and Delta variants in vitro, whereas the antiviral activity of EV053286 was moderate, but it had a wide-range of suppressive activity on the wild-type virus as well as the Alpha, Beta, Delta, Kappa, Omicron BA.1, and BA.2 variants. With the combined use of EV053273 and EV053286, we observed similar inhibitory effects on viral replication as with REGN-COV in vitro. We further assessed their activity in vivo by using a mouse model infected with a recently established viral strain with adopted infectious activity in mice. Independent experiments revealed that the combined use of EV053273 and EV053286 or the single use of each monoclonal antibody efficiently blocked infection in vivo. Together with data showing that these two monoclonal antibodies could neutralize REGN-COV escape variants and the Omicron variant, our findings suggest that the EV053273 and EV053286 monoclonal antibody cocktail is a novel clinically applicable therapeutic candidate for SARS-CoV-2 infection.
Keywords: Escape mutants; Neutralizing activity; Omicron variants; SARS-CoV-2; Spike protein; mAb.