Immunological Properties of SARS-CoV-2 S and M Protein Fragments and Their Effects on Respiratory Burst in Human Neutrophils.

The immune response to peptides derived from SARS-CoV-2 S and M proteins and their effects on NADPH oxidase-dependent generation of reactive species were explored. Peptides were selected based on B-cell epitope predictions, and their fusions with glutathione S-transferase were obtained. Such fusions containing fragments of the receptor binding domain (RBD) were recognized by IgG antibodies developed in COVID-19 patients with efficiency comparable to full-length RBD. The S673-713 peptide containing the furin cleavage site demonstrated the highest reactivity in samples from patients with mild COVID-19, suggesting a potential role in protective immune responses. Peptides with a high antibody recognition contained multiple protease cleavage sites, indicating a possible role for S protein processing in SARS-CoV-2 immunogenicity. Their effects on the generation of reactive species in blood and isolated neutrophils were investigated. Functionally, selected peptides (S672-875, S592-647, and S357-380) modulated the opsonized zymosan induced response in blood, whereas S673-713, S673-713 P681H, and M105-117 showed weaker effects. In isolated neutrophils, peptides containing fragments of RBD (S434-483) or the S1/S2 cleavage site (S673-713) enhanced phagocytosis-dependent, formyl peptide receptor (FPR)-mediated and PMA-induced production of reactive species. In contrast, the P681H mutation both decreased antibody recognition of S673-713 and removed or significantly reduced functional effects on blood neutrophils, suggesting a potential mechanism contributing to viral spread and immune evasion. These findings provide insight into how viral peptide fragments modulate innate immune responses via formyl peptide receptors and contribute to mechanisms of viral recognition.