Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. NAb responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. ABSTRACT Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1.1.7 and B.1.351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1.1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and membrane-directed T cell responses. These data shed light on the cross-neutralization of emerging variants by early pandemic convalescent immune responses. IMPORTANCE Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. NAb responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. However, SARS-CoV-2 variants are emerging that contain mutations in the spike gene that promote evasion from NAb responses. These variants may therefore delay control of the COVID-19 pandemic. We studied whether NAb responses from early COVID-19 convalescent patients are effective against the two SARS-CoV-2 variants, B.1.1.7 and B.1.351. We observed that the B.1.351 variant demonstrates significantly reduced susceptibility to early pandemic NAb responses. We additionally characterized virological, immunological, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.

[1]  Davey M. Smith,et al.  Sensitive immunodetection of SARS-CoV-2 variants-of-concern 501Y.V2 and 501Y.V1 , 2021, The Journal of infectious diseases.

[2]  J. Wrammert,et al.  Infection- and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant , 2021, Cell Host & Microbe.

[3]  N. Sullivan,et al.  Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine , 2021, The New England journal of medicine.

[4]  P. Dormitzer,et al.  Neutralizing Activity of BNT162b2-Elicited Serum , 2021, The New England journal of medicine.

[5]  M. Beer,et al.  SARS-CoV-2 spike D614G change enhances replication and transmission , 2021, Nature.

[6]  J. Rassen,et al.  Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection , 2021, JAMA internal medicine.

[7]  N. Landau,et al.  Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies , 2021, bioRxiv.

[8]  D. Burton,et al.  Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants , 2021, Science.

[9]  S. Atabani,et al.  S-variant SARS-CoV-2 lineage B1.1.7 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-qPCR , 2021, The Journal of infectious diseases.

[10]  B. Autran,et al.  SARS-CoV-2 variants and ending the COVID-19 pandemic , 2021, The Lancet.

[11]  D. Fremont,et al.  SARS-CoV-2 variants show resistance to neutralization by many monoclonal and serum-derived polyclonal antibodies , 2021, Research square.

[12]  P. Marrack,et al.  The basis of a more contagious 501Y.V1 variant of SARS-CoV-2 , 2021, Cell Research.

[13]  V. Gushchin,et al.  Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia , 2021, The Lancet.

[14]  D. Fremont,et al.  Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization , 2021, Cell Host & Microbe.

[15]  D. Ho,et al.  Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization , 2021, bioRxiv.

[16]  P. Dormitzer,et al.  Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera , 2021, Science.

[17]  K. Kupferschmidt Fast-spreading U.K. virus variant raises alarms. , 2020, Science.

[18]  J. Mascola,et al.  Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine , 2020, The New England journal of medicine.

[19]  D. Stuart,et al.  Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers , 2020, The New England journal of medicine.

[20]  R. Goldstein,et al.  Neutralising antibodies in Spike mediated SARS-CoV-2 adaptation , 2020, medRxiv.

[21]  Nguyen H. Tran,et al.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK , 2020, Lancet.

[22]  R. Tibshirani,et al.  Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome , 2020, Science Immunology.

[23]  D. Lauffenburger,et al.  Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques , 2020, Nature.

[24]  C. Cordon-Cardo,et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months , 2020, Science.

[25]  M. Malim,et al.  Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans , 2020, Nature Microbiology.

[26]  Vineet D. Menachery,et al.  Spike mutation D614G alters SARS-CoV-2 fitness , 2020, Nature.

[27]  A. Iafrate,et al.  Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients , 2020, Science Immunology.

[28]  J. Greenbaum,et al.  Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity , 2020, Cell.

[29]  M. Beltramello,et al.  Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology , 2020, Cell.

[30]  P. Sopp,et al.  Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19 , 2020, Nature Immunology.

[31]  Y. Wen,et al.  Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China , 2020, JAMA internal medicine.

[32]  S. Mallal,et al.  Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans , 2020, Science.

[33]  D. Lauffenburger,et al.  Single-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques , 2020, Nature.

[34]  D. Weissman,et al.  D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization , 2020, Cell Host & Microbe.

[35]  J. Sodroski,et al.  Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike , 2020, Nature.

[36]  Martin Linster,et al.  SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls , 2020, Nature.

[37]  S. Rowland-Jones,et al.  Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus , 2020, Cell.

[38]  Harnish Mukesh Naik,et al.  Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population , 2020, medRxiv.

[39]  Qiang Zhou,et al.  A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2 , 2020, Science.

[40]  D. Lauffenburger,et al.  Quick COVID-19 Healers Sustain Anti-SARS-CoV-2 Antibody Production , 2020, Cell.

[41]  J. Greenbaum,et al.  Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals , 2020, Cell.

[42]  G. Koh,et al.  Faculty Opinions recommendation of Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals , 2020, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.

[43]  M. V. van Breemen,et al.  Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability , 2020, Science.

[44]  E. Dong,et al.  An interactive web-based dashboard to track COVID-19 in real time , 2020, The Lancet Infectious Diseases.