key: cord-0870578-jpw1g95l authors: Edara, Venkata Viswanadh; Norwood, Carson; Floyd, Katharine; Lai, Lilin; Davis-Gardner, Meredith E.; Hudson, William H.; Mantus, Grace; Nyhoff, Lindsay E.; Adelman, Max W.; Fineman, Rebecca; Patel, Shivan; Byram, Rebecca; Gomes, Dumingu Nipuni; Michael, Garett; Abdullahi, Hayatu; Beydoun, Nour; Panganiban, Bernadine; McNair, Nina; Hellmeister, Kieffer; Pitts, Jamila; Winters, Joy; Kleinhenz, Jennifer; Usher, Jacob; O’Keefe, James B.; Piantadosi, Anne; Waggoner, Jesse J.; Babiker, Ahmed; Stephens, David S.; Anderson, Evan J.; Edupuganti, Srilatha; Rouphael, Nadine; Ahmed, Rafi; Wrammert, Jens; Suthar, Mehul S. title: Infection and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant date: 2021-03-20 journal: Cell Host Microbe DOI: 10.1016/j.chom.2021.03.009 sha: c1b5af5debc4842d0db5fd13cf854637a0b716da doc_id: 870578 cord_uid: jpw1g95l The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live virus neutralization of sera from naturally infected and Moderna vaccinated individuals against two SARS-CoV-2 variants, B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely-infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant. <239 -18544; Figure 1E ). We observed similar reductions in IgG binding titers to the B.1 and 118 B.1.351 RBD across these two timepoints (Figure 1F-G) . We next determined the impact on the 119 neutralization capacity of these samples across the two timepoints. At the 1-3-month timepoint, 120 we observed a 4.8-fold reduction (p<0.0001) in neutralization capacity between the B. vaccination. In addition, the recombinant RBD fragment used for the binding studies might be 211 different from the native confirmation found within the spike protein, which may influence 212 antibody binding and neutralization. It is possible that mutations outside the RBD could alter the 213 confirmation of the spike, resulting in increased or decreased sensitivity to neutralizing 214 antibodies. Another limitation is that the B.1.351 virus that we used in our study contains two 215 substitutions within the spike protein that were not reported in the reference sequence deposited 216 into GISAID (EPI_ISL_678615). One of these is a substitution of a Q677H, which has now been 217 reported in multiple lineages of circulating variants of SARS-CoV-2 in the US population as early 218 as mid-August 2020 (Hodcroft et al., 2021) . The other is a substitution (R682W) within the furin 219 cleavage motif (PRRAR) located between the S1/S2 regions of the spike protein. 466 Longitudinal analysis of humoral immunity against SARS-CoV-2 Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 476 Vaccine in Older Adults Metagenomic Sequencing To Detect 479 Respiratory Viruses in Persons under Investigation for COVID-19 Resistance of SARS-CoV-2 variants to 486 neutralization by monoclonal and serum-derived polyclonal antibodies Immunological memory to SARS-CoV-491 2 assessed for up to 8 months after infection Infection and mRNA-1273 495 vaccine antibodies neutralize SARS-CoV-2 UK variant & 498 ACHARYA, P. 2021. D614G Mutation Alters SARS-CoV-2 Spike Conformation and 499 Enhances Protease Cleavage at the S1/S2 Junction Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain 505 that Escape Antibody Recognition Emergence in late 2020 of 510 multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 511 677. medRxiv An mRNA Vaccine against SARS-CoV-2 -Preliminary Report Loss of furin cleavage 527 site attenuates SARS-CoV-2 pathogenesis Viridot: An automated virus 531 plaque (immunofocus) counter for the measurement of serological neutralizing 532 responses with application to dengue virus SARS-CoV-2 D614G 535 spike mutation increases entry efficiency with enhanced ACE2-binding affinity Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike 547 Receptor-Binding Domain by Structure-Guided High-Resolution Serology & 555 MENACHERY, V. D. 2021. The Variant Gambit: COVID's Next Move Stable 562 neutralizing antibody levels six months after mild and severe COVID-19 episode & 568 SCHOTSAERT, M. 2021. The N501Y mutation in SARS-CoV-2 spike leads to morbidity 569 in obese and aged mice and is neutralized by convalescent and post-vaccination human 570 sera Antibody potency, effector 575 function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo 580 SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by 581 ancestral Spike vaccines Persistence of SARS-CoV-2 specific B-and T-cell responses Neutralizing and protective human monoclonal antibodies 603 recognizing the N-terminal domain of the SARS-CoV-2 spike protein Rapid Generation of 612 Neutralizing Antibody Responses in COVID-19 Patients Emergence and rapid spread of a new severe acute respiratory syndrome-related 623 coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa Development of a Rapid Focus Reduction 628 Neutralization Test Assay for Measuring SARS-CoV-2 Neutralizing Antibodies Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein SARS-CoV-2 501Y.V2 escapes neutralization by 638 South African COVID-19 donor plasma Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination Human neutralizing antibodies against SARS-CoV-2 require 651 intact Fc effector functions and monocytes for optimal therapeutic protection Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine -657 Preliminary Report Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K, and 661 N501Y variants by BNT162b2 vaccine-elicited sera