tetano
Editor, Senior Moderator
JCI Insight
. 2021 Mar 26;147386.
doi: 10.1172/jci.insight.147386. Online ahead of print.
IgV somatic mutation of human anti-SARS-CoV-2 monoclonal antibodies governs neutralization and breadth of reactivity
Mayara Garcia de Mattos Barbosa[SUP] 1 [/SUP], Hui Liu[SUP] 1 [/SUP], Daniel Huynh[SUP] 1 [/SUP], Greg Shelley[SUP] 2 [/SUP], Evan T Keller[SUP] 2 [/SUP], Brian T Emmer[SUP] 3 [/SUP], Emily J Sherman[SUP] 3 [/SUP], David Ginsburg[SUP] 4 [/SUP], Andrew A Kennedy[SUP] 3 [/SUP], Andrew W Tai[SUP] 3 [/SUP], Christiane E Wobus[SUP] 5 [/SUP], Carmen Mirabelli[SUP] 5 [/SUP], Thomas M Lanigan[SUP] 6 [/SUP], Milagros Samaniego[SUP] 7 [/SUP], Wenzhao Meng[SUP] 8 [/SUP], Aaron M Rosenfeld[SUP] 8 [/SUP], Eline T Luning Prak[SUP] 9 [/SUP], Jeffrey L Platt[SUP] 1 [/SUP], Marilia Cascalho[SUP] 5 [/SUP]
Affiliations
Abstract
Antibodies that neutralize SARS-CoV-2, are thought to provide the most immediate and effective treatment for those severely afflicted by this virus. Because coronavirus potentially diversifies by mutation, broadly neutralizing antibodies are especially sought. Here we report a novel approach to rapid generation of potent broadly neutralizing human anti-SARS-CoV-2 antibodies. We isolated SARS-CoV-2 Spike protein-specific memory B cells by panning from the blood of convalescent human subjects after infection with SARS-CoV-2, sequenced and expressed Ig genes from individual B cells as human monoclonal antibodies (mAbs). All of 43 human mAbs generated in this way neutralized SARS-CoV-2. Eighteen of the 43 human mAbs exhibited half-maximal inhibitory concentration (IC50s) of 6.7 x10-12 M to 6.7x10-15 M for spike pseudotyped virus. Seven of the human mAbs also neutralized with IC50<6.7 x10-12 M viruses pseudotyped with mutant spike proteins (including receptor binding domain mutants and the S1 C-terminal D614G mutant). Neutralization of the Wuhan Hu-1 founder strain and of some variants decreased when coding sequences were reverted to germline, suggesting that potency of neutralization was acquired by somatic hypermutation and selection of B cells. The results indicate that infection with SARS-CoV-2 evokes high affinity B cell responses, some products of which are broadly neutralizing and others highly strain-specific. We also identify variants that would potentially resist immunity evoked by infection with the Wuhan Hu-1 founder strain or by vaccines developed with products of that strain, suggesting evolutionary courses SARS-CoV-2 could take.
Keywords: COVID-19; Immunoglobulins; Immunology; Molecular biology.
. 2021 Mar 26;147386.
doi: 10.1172/jci.insight.147386. Online ahead of print.
IgV somatic mutation of human anti-SARS-CoV-2 monoclonal antibodies governs neutralization and breadth of reactivity
Mayara Garcia de Mattos Barbosa[SUP] 1 [/SUP], Hui Liu[SUP] 1 [/SUP], Daniel Huynh[SUP] 1 [/SUP], Greg Shelley[SUP] 2 [/SUP], Evan T Keller[SUP] 2 [/SUP], Brian T Emmer[SUP] 3 [/SUP], Emily J Sherman[SUP] 3 [/SUP], David Ginsburg[SUP] 4 [/SUP], Andrew A Kennedy[SUP] 3 [/SUP], Andrew W Tai[SUP] 3 [/SUP], Christiane E Wobus[SUP] 5 [/SUP], Carmen Mirabelli[SUP] 5 [/SUP], Thomas M Lanigan[SUP] 6 [/SUP], Milagros Samaniego[SUP] 7 [/SUP], Wenzhao Meng[SUP] 8 [/SUP], Aaron M Rosenfeld[SUP] 8 [/SUP], Eline T Luning Prak[SUP] 9 [/SUP], Jeffrey L Platt[SUP] 1 [/SUP], Marilia Cascalho[SUP] 5 [/SUP]
Affiliations
- PMID: 33769311
- DOI: 10.1172/jci.insight.147386
Abstract
Antibodies that neutralize SARS-CoV-2, are thought to provide the most immediate and effective treatment for those severely afflicted by this virus. Because coronavirus potentially diversifies by mutation, broadly neutralizing antibodies are especially sought. Here we report a novel approach to rapid generation of potent broadly neutralizing human anti-SARS-CoV-2 antibodies. We isolated SARS-CoV-2 Spike protein-specific memory B cells by panning from the blood of convalescent human subjects after infection with SARS-CoV-2, sequenced and expressed Ig genes from individual B cells as human monoclonal antibodies (mAbs). All of 43 human mAbs generated in this way neutralized SARS-CoV-2. Eighteen of the 43 human mAbs exhibited half-maximal inhibitory concentration (IC50s) of 6.7 x10-12 M to 6.7x10-15 M for spike pseudotyped virus. Seven of the human mAbs also neutralized with IC50<6.7 x10-12 M viruses pseudotyped with mutant spike proteins (including receptor binding domain mutants and the S1 C-terminal D614G mutant). Neutralization of the Wuhan Hu-1 founder strain and of some variants decreased when coding sequences were reverted to germline, suggesting that potency of neutralization was acquired by somatic hypermutation and selection of B cells. The results indicate that infection with SARS-CoV-2 evokes high affinity B cell responses, some products of which are broadly neutralizing and others highly strain-specific. We also identify variants that would potentially resist immunity evoked by infection with the Wuhan Hu-1 founder strain or by vaccines developed with products of that strain, suggesting evolutionary courses SARS-CoV-2 could take.
Keywords: COVID-19; Immunoglobulins; Immunology; Molecular biology.