Global profiling of SARS-CoV-2 specific IgG/ IgM responses of convalescents using a proteome microarray

Abstract

COVID-19 is caused by SARS-CoV-2, and has become a global pandemic. There is no highly effective medicine or vaccine, most of the patients were recovered by their own immune response, especially the virus specific IgG and IgM responses. However, the IgG/ IgM responses is barely known. To enable the global understanding of SARS-CoV-2 specific IgG/ IgM responses, a SARS-CoV-2 proteome microarray with 18 out of the 28 predicted proteins was constructed. The microarray was applied to profile the IgG/ IgM responses with 29 convalescent sera. The results suggest that at the convalescent phase 100% of patients had IgG/ IgM responses to SARS-CoV-2, especially to protein N, S1 but not S2. S1 purified from mammalian cell demonstrated the highest performance to differentiate COVID-19 patients from controls. Besides protein N and S1, significant antibody responses to ORF9b and NSP5 were also identified. Indepth analysis showed that the level of S1 IgG positively correlate to age and the level of LDH (lactate dehydrogenase), especially for women, while the level of S1 IgG negatively correlate to Ly% (Lymphocyte percentage). This study presents the first whole picture of the SARS-CoV-2 specific IgG/ IgM responses, and provides insights to develop precise immuno-diagnostics, effective treatment and vaccine. Highlights• A SARS-CoV-2 proteome microarray contains 18 of the 28 predicted proteins• The 1 st global picture of the SARS-CoV-2 specific IgG/ IgM response reveals that at the convalescent phase, 100% of patients have IgG/ IgM responses to protein N and S1• Significant antibody responses against ORF9b and NSP5 were identified • Protein S1 specific IgG positively correlates to age and LDH, while negatively to Ly%

Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

“…COVA1-21 also efficiently blocked virus infection, suggesting an alternative mechanism of neutralization than blocking ACE2 engagement. Overall, our data are consistent with the previous identification of multiple antigenic RBD sites for SARS-CoV-2 and additional non-RBD sites on the S protein as described for SARS-CoV and MERS-CoV (29,38). Here, our discovery of non-RBD-targeting mAbs provides additional depth to the definition of antibody epitopes on the SARS-CoV-2 S protein.…”

Antigenic variation of SARS-CoV-2 in response to immune pressure

“…Overall, these data fit very well with the observation that most humoral immune responses against SARS-CoV-2 and other human coronaviruses are directed against the S and N proteins (Farrera et al, 2020;Jiang et al, 2020;Poh et al, 2020). These results also support the notion that the selective pressure exerted by the human antibody response is already detectable in the SARS-CoV-2 population.…”

“…These works, as well as others (Farrera et al, 2020;Poh et al, 2020), revealed that the cell-mediated responses against SARS-CoV-2 are not restricted to the nucleocapsid (N) and spike (S) proteins, but rather target both structural and non-structural viral products. In parallel, analyses of B cell responses in SARS-CoV-2 infected patients showed that the S and N proteins are the major target of the antibody response and identified specific B cell epitopes in the S protein (Farrera et al, 2020;Jiang et al, 2020;Poh et al, 2020). We exploited this growing wealth of information to investigate whether, after a few months of sustained transmission, the selective pressure exerted by the human adaptive immune response is already detectable in the SARS-CoV-2 population and to investigate how the virus is evolving in response to such a pressure.…”

SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors

“…In hospitalized patients, seroconversion is typically detected between 5-14 days post symptom onset, with a median time of 5-12 days for anti-S IgM and 14 days for IgG and IgA 6,7,[13][14][15][16] . The kinetics of anti-N response was described to be similar to that of anti-S, although N responses might appear earlier [15][16][17] . Anti-SARS-CoV-2 antibody titers correlate with disease severity, likely reflecting higher viral replication rates and/or immune activation in patients with severe outcome.…”

“…Anti-SARS-CoV-2 antibody titers correlate with disease severity, likely reflecting higher viral replication rates and/or immune activation in patients with severe outcome. Besides N and S, antibody responses to other viral proteins (mainly ORF9b and NSP5) were also identified by antibody microarray 17 .…”