In a recent article published in scientific reports, researchers performed immunoglobulin (Ig)M and IgG epitope mapping against 487 peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These peptides encompassed four major structural proteins of SARS-CoV-2, namely spike glycoprotein (S), envelope (E), nucleocapsid (N), and membrane (M) proteins.
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Investigation of humoral immune responses in ethnically diverse populations representing the different clinical profiles of coronavirus disease 2019 (COVID-19) could help better define correlates of protection. Furthermore, it could aid the development of more effective serological diagnostic assays and COVID-19 vaccines tailored for such populations. Due to its limited availability and ineffectiveness against new variants of SARS-CoV-2 (eg, Omicron), the COVID-19 pandemic continues to wreak havoc around the world almost three years after it began.
About the study
In the present study, the researchers conducted a large antibody epitope mapping study among patients infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR) from two African countries, Senegal and Madagascar. . They also determined the primary B-cell epitopes recognized by these SARS-CoV-2-infected African patients.
The study population comprised 65 and 16 (82 total) SARS-CoV-2-infected patients and 32 and 10 (=41) uninfected individuals from Senegal and Madagascar, respectively. The investigators collected serum samples from these two groups and assessed whether their different distributions of IgM and IgG epitopes explained their different clinical profiles of COVID-19. In addition, they compared the results with previous studies from Europe, Asia, and the United States of America (USA).
The serum samples used in the study were from patients of different ethnic origins and different disease profiles, namely asymptomatic, symptomatic, and severe COVID-19.
Study findings
Study analysis confirmed that all identified IgG epitopes represented immunodominant epitopes. Previous studies from different continents have similarly identified five and eight IgG epitope regions in the N and S domains. Most of the immunodominant IgG epitopes were nested outside the N-terminal and receptor-binding domain (RBD) regions. and NTD) of the SARS-CoV-2 S protein, the known center for most SARS-CoV-2 mutations. Interestingly, many of these immunodominant peptide epitopes are proven targets of neutralizing antibodies, eg, S139/140, S165, S204, and S287/288. In addition, the investigators found several immunodominant epitopes for IgM, perhaps because they collected serum samples 10 to 12 days after symptom onset. However, they did not find immunodominant epitopes on the SARS-CoV-2 E protein in this study, as in previous studies.
Furthermore, the observed humoral responses to SARS-CoV-2 in people from Madagascar and Senegal were quite comparable, with some differences due to different patient profiles at the time of sampling. The samples belonged to patients with early or late-stage SARS-CoV-2 infections. Consequently, asymptomatic patients had more IgM epitopes and those with severe COVID-19 switched to IgG epitopes due to prolonged exposure to SARS-CoV-2. Based on IgG and IgM scores, even earlier studies have shown a stronger immune response in severely ill COVID-19 patients compared to their asymptomatic or symptomatic counterparts.
Another important observation made by the researchers was that some severely ill patients no longer had a detectable burden of SARS-CoV-2 at the time of study sampling. In addition, those with a higher neutralizing antibody score had a lower viral load, suggesting that their humoral response may have cleared the virus but failed to help them survive. Patients in the severe group were older than the symptomatic and asymptomatic groups, with greater susceptibility to COVID-19.
conclusions
Overall, the analysis of the present study confirmed that the picture of the humoral immune response of African patients to SARS-CoV-2 was comparable to that of other continents, indicating little or no effect of diversity of ethnicity and genetic background. of these populations.
A group of 36 peptides nested within the SARS-CoV-2 S and N structural proteins exhibited the highest reactivity to neutralizing antibodies. In particular, the patients’ IgM, IgM/IgG, and IgG were assigned to nine, two, and 25 SARS-CoV-2 peptides, respectively. The immunodominant IgG epitopes identified were similar to those described in Asian, European, and US studies. These immunodominant epitopes could aid the development of novel and more effective vaccine candidates and rapid serological diagnostic assays.
The present study did not determine the role of T cells, a critical component of the humoral immune response to SARS-CoV-2. The lack of an adequate induction of the T cell response led to the death of some severely ill patients who developed an adequate humoral response. It might be interesting if future studies identify peptides recognized by T cells in these African patients.
