Understanding the course of the antibody response directed to individual
epitopes of SARS-CoV-2
proteins is crucial for serological assays and establishment of
vaccines. Twenty-one synthetic
peptides were synthesized that have ten
amino acids overlap and cover the complete membrane (M)
protein. Plasma samples from 32 patients having
acute disease and 30 patients from the convalescent phase were studied. Only
peptide M01 (aa 1-20) and to a lesser extent
peptide M21 (aa 201-222) showed specific reactivity as compared to historical control plasma samples.
Peptide M01 was recognized by
IgM- (71.9%) and
IgG-specific
antibodies (43.8%) during the acute phase as early as day 8 PIO. In a longitudinal analysis, a higher reactivity was observed for the
IgM response directed to
peptide M01 following day 20 PIO as compared to earlier time points of the acute phase. In the convalescent phase, antibody reactivity to the two M-specific
peptides was significantly lower (<30% seropositivity). A fusion
protein encoding major parts of RBD also showed higher rates of recognition during acute (50.0%) and lower rates in the convalescent phase (23.3%). Taken together, our results suggest that during the acute phase of
COVID-19 antibodies are raised to two linear
epitopes of the SARS-CoV-2 M
protein, located at the very N- and C-termini, showing almost similar levels of reactivity as immunodominant linear
epitopes derived from the spike and
nucleocapsid protein. Anti-M is also present in the convalescent phase of
COVID-19 patients, however at lower levels, with the N-terminus of the M
protein as a preferred target.