Non-neutralizing Antibodies Induced by Spike Protein Can Negatively Affect CNS






Study: Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice

Published: April 2023, Frontiers in Molecular Neuroscience

A study investigated the impact of non-neutralizing anti-S1-111 IgG antibodies, induced by the spike protein of SARS-CoV-2, on the central nervous system (CNS) in mice. The mice were immunized with spike-protein-derived peptides or a control protein, and their behavior, antibody levels, glial cell state, gene expression, and cognitive function were assessed.

The study found that the non-neutralizing antibody increased the density of microglia and activated microglia and astrocytes in the hippocampus, leading to a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among the mice.

Transcriptome profiling revealed up-regulated genes in the mice associated with synaptic plasticity and mental disorders. These findings suggest that preventing the production of non-neutralizing antibodies may reduce CNS manifestations in COVID-19 patients and vaccinated individuals.

COVID-19, vaccine, central nervous system, non-neutralizing antibodies, spike protein, glial cells, synaptic plasticity, mental disorders, psychosis

What I found interesting:
The researchers used an APOE-/- model, similar to APOE E4 allele, for this study.

Non-neutralizing antibodies are common in the sera of COVID-19 patients. While antibodies against the receptor binding domain (RBD) of the spike protein can neutralize the virus, most antibodies in COVID-19 patients are non-neutralizing. Non-neutralizing antibodies can cause antibody-dependent cytotoxicity (ADCC), but they can also cause antibody-dependent enhancement (ADE) and pro-inflammatory effects.  Researchers have detected anti-SARS-CoV-2 antibodies in the cerebrospinal fluid of COVID-19 patients with encephalopathy, indicating that these antibodies can cross the blood-brain barrier and cause mental disorders through molecular mimicry or other mechanisms.