2021
DOI: 10.1101/2021.08.02.454546
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Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern

Abstract: Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remained effective against emerging variants of concern in vitro and in vivo. CV3-1 bound to the (485-G… Show more

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Cited by 11 publications
(7 citation statements)
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References 113 publications
(148 reference statements)
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“…This finding is of significance, as emerging variants of concern and of interest display fewer mutations in the S2 subunit compared with the S1. Indeed, CV3-25 can efficiently neutralize the B.1.351 variant, while neutralization by anti-NTD and anti-RBD NAbs was greatly diminished (Li et al, 2021a;Stamatatos et al, 2021) Hence, epitopes in S2 targeted by CV3-25 can be explored to generate future antigenic templates for potent pan-coronavirus antibodies (Sauer et al, 2021).…”
Section: Discussionmentioning
confidence: 99%
“…This finding is of significance, as emerging variants of concern and of interest display fewer mutations in the S2 subunit compared with the S1. Indeed, CV3-25 can efficiently neutralize the B.1.351 variant, while neutralization by anti-NTD and anti-RBD NAbs was greatly diminished (Li et al, 2021a;Stamatatos et al, 2021) Hence, epitopes in S2 targeted by CV3-25 can be explored to generate future antigenic templates for potent pan-coronavirus antibodies (Sauer et al, 2021).…”
Section: Discussionmentioning
confidence: 99%
“…Neutralization plays a crucial role in protection against SARS-CoV-2 infection. Therefore many studies have focused on neutralization responses from convalescent plasma Beaudoin-Bussieres et al, 2020;Gasser et al, 2021;Long et al, 2020;Prevost et al, 2020;Robbiani et al, 2020), vaccine-elicited antibodies (ClinicalTrials.gov: NCT04516746, NCT04368728, NCT04505722, NCT04470427; Baden et al, 2021;Polack et al, 2020;Skowronski and De Serres, 2021;Tauzin et al, 2021), and cocktails of mAbs for use as therapeutics (Hurlburt et al, 2020;Jennewein et al, 2021;Ju et al, 2020;Li et al, 2021b;Liu et al, 2020;Schafer et al, 2021;Tian et al, 2020;Wu et al, 2020b;Yuan et al, 2020). However, antibodies are polyvalent molecules able to mediate several antiviral functions (Adeniji et al, 2021).…”
Section: Discussionmentioning
confidence: 99%
“…Considerable effort has been made to study antibody-mediated neutralization and its effect in mitigating SARS-CoV-2 infection. Many neutralizing antibodies target the RBD, but some targeting the NTD and the S2 subunits were reported (Cao et al, 2020;Chen et al, 2020;Chi et al, 2020;Jennewein et al, 2021;Ju et al, 2020;Li et al, 2021b;Liu et al, 2020;Rappazzo et al, 2021;Seydoux et al, 2020;Suryadevara et al, 2021;Ullah et al, 2021a;Voss et al, 2021;Wang et al, 2020;Wrapp et al, 2020a;Wu et al, 2020b;Yuan et al, 2020). Some studies have shown that around 25%-45% of people who resolve the infection have plasma with low or undetectable levels of SARS-CoV-2 neutralizing activity (Beaudoin-Bussieres et al, 2020;Luchsinger et al, 2020;Muecksch et al, 2021;Payne et al, 2020;Prevost et al, 2020;Robbiani et al, 2020;Wu et al, 2020a).…”
Section: Introductionmentioning
confidence: 99%
“…Finally, the SH-H epitope region we describe is in the stem helix, a region known to be highly conserved across coronaviruses. Broadly neutralizing [ 77 79 ] stem helix antibodies have been isolated and suggest an avenue for rational design of a pan-coronavirus vaccine. Interestingly, a mAb raised against the MERS-CoV stem region protected mice against SARS-CoV-2 challenge, despite having no neutralizing activity against SARS-CoV-2 in vitro [ 80 ].…”
Section: Discussionmentioning
confidence: 99%