A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site

Onodera, Taishi; Kita, Shunsuke; Adachi, Yu; Moriyama, Saya; Sato, Akihiko; Nomura, Takao; Sakakibara, Shuhei; Inoue, Takeshi; Tadokoro, Takashi; Anraku, Yuki; Yumoto, Kohei; Tian, Cong; Fukuhara, Hideo; Sasaki, Michihito; Orba, Yasuko; Shiwa, Nozomi; Iwata, Naoko; Nagata, Noriyo; Suzuki, Tateki; Sasaki, Jiei; Sekizuka, Tsuyoshi; Tonouchi, Keisuke; Sun, Lin; Fukushi, Shuetsu; Satofuka, Hiroyuki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Kurosaki, Tomohiro; Kuroda, Makoto; Matsuura, Yoshiharu; Suzuki, Tadaki; Hanabusa, Takao; Maenaka, Katsumi; Takahashi, Yoshimasa

doi:10.1016/j.immuni.2021.08.025

Cited by 50 publications

(39 citation statements)

References 87 publications

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“…Thus, it was the cumulative effect of several mutations that abrogated antiviral activity of the other monoclonal antibodies. REGN10933 (Casirivamab), the neutralizing activity of which has been previously found to be affected by E484K and K417N of the Beta spike protein, 4 , 40 , 41 is decreased another 8-fold by E484A of Omicron. REGN10987 (Imdevimab), which is nearly impervious to mutations in the earlier VOCs, was compromised by four Omicron mutations (S371L, S373P, N440K, G446S).…”

Section: Discussionmentioning

confidence: 99%

Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

et al. 2022

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“…Our study demonstrated a possibility to develop a heterologous prime-boost vaccine strategy for a universal vaccine that can protect against a broad spectrum of SARS-related coronaviruses. A recent report also showed that in mice, sequential immunization S/RBD vaccine of SARS-CoV, SARS-CoV-2, and MERS-CoV led to induction of cross-reactive antibodies and isolation of monoclonal antibodies with broadly neutralizing activities [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Broad and durable antibody response after vaccination with inactivated SARS-CoV-2 in individuals with a history of 2003 SARS-CoV infection

Huang

Zheng

Wang

et al. 2022

Emerging Microbes & Infections

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In vaccinees who were infected with SARS-CoV in 2003, we observed greater antibody responses against spike and nucleoprotein of both SARS-CoV-2 and SARS-CoV after a single dosage of inactivated SARS-CoV-2 vaccine. After receiving the second vaccination, antibodies against RBD of SARS-CoV-2 Wuhan, Beta, Delta, and recently emerged Omicron are significantly higher in SARS-CoV experienced vaccinees than in SARS-CoV naïve vaccinees. Neutralizing activities measured by authentic viruses and pseudoviruses of SARS-CoV, SARS-CoV-2 Wuhan, Beta, and Delta are greater in SARS-CoV experienced vaccinees. In contrast, only weak neutralizing activities against SARS-CoV-2 and variants were detected in SARS-CoV naïve vaccinees. By 6 months after the second vaccination, neutralizing activities were maintained at a relatively higher level in SARS-CoV experienced vaccinees but were undetectable in SARS-CoV naïve vaccinees. These findings suggested a great possibility of developing a universal vaccine by heterologous vaccination using spike antigens from different SARS-related coronaviruses.

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“…For pandemic preparedness, pan-sarbecovirus therapeutics and vaccines that are effective against future SARS-CoV-2 variants and other sarbecoviruses are urgently needed 11–14 . Several broad sarbecovirus neutralizing antibodies have been reported 20,23–34 ; however, since the number of antibodies studied has been limited, we still lack a comprehensive understanding of the RBD epitopes that could induce broad sarbecovirus neutralizing antibodies.…”

Section: Mainmentioning

confidence: 99%

Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies

Cao

Yisimayi

Jian

et al. 2022

Preprint

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Constantly emerging SARS-CoV-2 variants, such as Omicron BA.1, BA.1.1 and BA.2, pose a severe challenge to COVID-19 control. Broad-spectrum antibody therapeutics and vaccines are needed for defending against future SARS-CoV-2 variants and sarbecovirus pandemics; however, we have yet to gain a comprehensive understanding of the epitopes capable of inducing broad sarbecovirus neutralization. Here, we report the identification of 241 anti-RBD broad sarbecovirus neutralizing antibodies isolated from 44 SARS-CoV-2 vaccinated SARS convalescents. Neutralizing efficacy of these antibodies against D614G, SARS-CoV-1, Omicron variants (BA.1, BA.1.1, BA.2), RATG13 and Pangolin-GD is tested, and their binding capability to 21 sarbecovirus RBDs is measured. High-throughput yeast-display mutational screening was further applied to determine each antibody's RBD escaping mutation profile, and unsupervised epitope clustering based on escaping mutation hotspots was performed. A total of 6 clusters of broad sarbecovirus neutralizing antibodies with diverse breadth and epitopes were identified, namely Group E1 (S309, BD55-3152 site), E3 (S2H97 site), F1 (CR3022, S304 site), F2 (DH1047, BD55-3500 site), F3 (ADG-2, BD55-3372 site) and B' (S2K146 site). Members of E1, F2 and F3 demonstrate the highest neutralization potency; yet, Omicron, especially BA.2, has evolved multiple mutations (G339D, N440K, T376A, D405N, R408S) to escape antibodies of these groups. Nevertheless, broad sarbecovirus neutralizing antibodies that survived Omicron would serve as favorable therapeutic candidates. Furthermore, structural analyses of selected drug candidates propose two non-competing antibody pairing strategies, E1-F2 and E1-F3, as broad-spectrum antibody cocktails. Together, our work provides a comprehensive epitope map of broad sarbecovirus neutralizing antibodies and offers critical instructions for designing broad-spectrum vaccines.

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A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site

Cited by 50 publications

References 87 publications

Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

Broad and durable antibody response after vaccination with inactivated SARS-CoV-2 in individuals with a history of 2003 SARS-CoV infection

Omicron BA.2 specifically evades broad sarbecovirus neutralizing antibodies

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