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Updated: Nov 24, 2025

Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
Biological Significance of Anti-SARS-CoV-2 Antibodies: Lessons Learned From Progressive Multifocal
Navid Manouchehri1, Lawrence Steinman1, Olaf Stuve2
1From the Department of Neurology (N.M.), the University of Texas Southwestern Medical Center, Dallas; Departments of Pediatrics and Neurology and Neurological Sciences (L.S.), Stanford University, CA; and Neurology Section (O.S.), VA North Texas Health Care System, Medical Service Dallas, VA Medical Center.
Objective:
To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML).
Methods:
Review of pertinent literature. RESULTS: There is at least 1 precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4+ T cells. PML is an infection of the CNS caused by JC virus (JCV), which commonly occurs during treatment with the therapeutic monoclonal antibody natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defense against JCV appear to be T cells. T cell-mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response.
Conclusion:
Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2-specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.

