{"id":127751,"date":"2021-09-17T03:22:23","date_gmt":"2021-09-17T10:22:23","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2021\/09\/bispecific-antibodies-targeting-distinct-regions-of-the-spike-protein-potently-neutralize-sars-cov-2-variants-of-concern"},"modified":"2021-09-17T03:22:23","modified_gmt":"2021-09-17T10:22:23","slug":"bispecific-antibodies-targeting-distinct-regions-of-the-spike-protein-potently-neutralize-sars-cov-2-variants-of-concern","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2021\/09\/bispecific-antibodies-targeting-distinct-regions-of-the-spike-protein-potently-neutralize-sars-cov-2-variants-of-concern","title":{"rendered":"Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/bispecific-antibodies-targeting-distinct-regions-of-the-spike-protein-potently-neutralize-sars-cov-2-variants-of-concern2.jpg\"><\/a><\/p>\n<p>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of existing vaccines and therapeutic antibodies and underscores the need for additional antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells collected from patients with coronavirus disease 2019. The three most potent antibodies targeted distinct regions of the receptor-binding domain (RBD), and all three neutralized the SARS-CoV-2 Alpha and Beta variants. The crystal structure of the most potent antibody, CV503, revealed that it binds to the ridge region of SARS-CoV-2 RBD, competes with the angiotensin converting enzyme 2 receptor, and has limited contact with key variant residues K417, E484 and N501. We designed bispecific antibodies by combining non-overlapping specificities and identified five bispecific antibodies that inhibit SARS-CoV-2 infection at concentrations of less than 1 ng\/mL. Through a distinct mode of action, three bispecific antibodies cross-linked adjacent spike proteins using dual N-terminal domain-RBD specificities. One bispecific antibody was greater than 100-fold more potent than a cocktail of its parent monoclonals in vitro and prevented clinical disease in a hamster model at a 2.5 mg\/kg dose. Notably, two bispecific antibodies in our panel comparably neutralized the Alpha, Beta, Gamma and Delta variants and wild-type virus. Furthermore, a bispecific antibody that neutralized the Beta variant protected hamsters against SARS-CoV-2 expressing the E484K mutation. Thus, bispecific antibodies represent a promising next-generation countermeasure against SARS-CoV-2 variants of concern.<\/p>\n<hr>\n<p>Bispecific antibodies targeting multiple regions of the SARS-CoV-2 spike protein comparably neutralize variants of concern and wild-type virus.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of existing vaccines and therapeutic antibodies and underscores the need for additional antibody-based tools that potently neutralize variants by targeting multiple sites of the spike protein. We isolated 216 monoclonal antibodies targeting SARS-CoV-2 from plasmablasts and memory B cells [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[],"class_list":["post-127751","post","type-post","status-publish","format-standard","hentry","category-biotech-medical"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/127751","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=127751"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/127751\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=127751"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=127751"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=127751"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}