Serological Markers of SARS-CoV-2 Reinfection

mBio

Pardis Sabeti¹  Sameed M. Siddiqui²  Douglas A. Lauffenburger³  Lacy M. Simons⁴  Judd F. Hultquist⁴  Ramon Lorenzo-Redondo⁴  Eric J. Nilles⁴  Egon A. Ozer⁴  Natasha Halasa⁵  Rana Talj⁵  Danielle A. Rankin⁵  Ahmad Yanis⁵  Hendrik Streeck⁶  Alex L. Zhu⁷  Matthew J. Gorman⁷  Stephanie Fischinger⁷  Yannic C. Bartsch⁷  Kathryn A. Bowman⁷  Dan H. Barouch⁷  Caroline Atyeo⁷  Galit Alter⁷  Jenny S. Maron⁷  Lindsay Chapman⁸  Suzanne Siebert⁸  Kyle Meade⁸  Sean Mullane⁸  Jordan Steinhart⁸  Anil S. Menon⁸  Elon R. Musk⁸  Samuel Beger⁸ 

[1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA;Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA;Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA;Institute of Virology, University Hospital, University of Bonn, and German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany;Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA;Space Exploration Technologies Corp., Hawthorne, California, USA;

关键词: SARS-CoV-2;    reinfection;    antibodies;    humoral immunity;    diagnostics;    biomarkers;   

DOI  :  10.1128/mbio.02141-21

来源: DOAJ

【 摘 要 】

ABSTRACT As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

【 授权许可】

Unknown