SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.

Jenna J Guthmiller,Florian Krammer,Ya-Nan Dai,Jiaolong Wang,Olivia Stovicek,Haley L Dugan,Min Huang,Christopher A Nelson,Jessica S Donington,Lei Li,Kumaran Shanmugarajah,Peter Halfmann,Yoshihiro Kawaoka,Daved H Fremont,Siriruk Changrob,Paige D Hall,Patrick C Wilson,Christopher T Stamper,Henry A Utset ,Nai Ying Zheng ,William Miller ,Maria Lucia L Madariaga ,Maud O Jansen ,Vera Tešić ,A Joachimiak

doi:10.1128/mbio.02940-20

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.IMPORTANCE With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein. Subjects who mounted a larger response against the spike also mounted antibody responses against other viral antigens, including the nucleocapsid protein and ORF8. Additionally, this study reveals that subjects with more severe disease mount a larger memory B cell response against the spike. These data suggest that subjects with more severe COVID-19 disease are likely better protected from reinfection with SARS-CoV-2.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic
Our understanding of the specificity of the antibody response against SARS-CoV-2 is rapidly expanding [5, 6], little is known about how coronavirus disease 2019 (COVID-19) severity relates to magnitude of both the secreted antibody and memory B cell (MBC) response
Our data indicate that subjects with more severe disease mount a larger antibody response, which corresponds with increased neutralizing antibody titers, MBC formation against the spike protein, and cross-reactive antibodies against conserved epitopes of the receptor-binding domain (RBD)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. Our understanding of the specificity of the antibody response against SARS-CoV-2 is rapidly expanding [5, 6], little is known about how coronavirus disease 2019 (COVID-19) severity relates to magnitude of both the secreted antibody and memory B cell (MBC) response. To address these critically important knowledge gaps, we collected plasma samples from SARS-CoV-2 acutely infected and convalescent subjects [7] and examined specificity of the humoral immune response. Our study indicates that the magnitude of the humoral immune response is related to infection severity

Methods

Results

Conclusion