Cyclic mapping reveals humoral responses against key structural proteins of SARS-CoV-2 in infected patients from Africa.


In a recently published article in Scientific reportsIn this study, the researchers performed epitope mapping of immunoglobulin (Ig)M and IgG against 487 peptides caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These peptides comprise four major structural proteins of SARS-CoV-2, that is, spike (S). glycoproteinenvelope (E), nucleocapsid (N), and membrane proteins (M).

Study: Linear epitope mapping of the humoral response against SARS-CoV-2 in two independent African cohorts.  Image credit: MedMoMedia/Shutterstock
Stady: Linear epitope mapping of the humoral response against SARS-CoV-2 in two independent African cohorts. Image credit: MedMoMedia/Shutterstock

background

Investigating humoral immune responses in ethnically diverse populations while taking into account the changing clinical features of coronavirus disease 2019 (COVID-19) can help better define protection relationships. Furthermore, it could help develop more effective serodiagnostic assays and adapted COVID-19 vaccines for such populations. Due to its limited availability and ineffectiveness against novel SARS-CoV-2 variants (eg, Omicron), the COVID-19 pandemic continues to wreak havoc globally after nearly three years since its inception.

about studying

In this study, the researchers conducted a large-scale antibody epitope mapping study among reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2-infected patients from two African countries, Senegal and Madagascar. They also identified the epitopes of primary B cells that were identified by these African patients with SARS-CoV-2.

The study population consisted of 65 and 16 (82 total) SARS-CoV-2-infected patients and 32 and 10 (=41) uninfected individuals from Senegal and Madagascar, respectively. The researchers collected serum samples from these two groups and assessed whether their variable IgM and IgG distributions explained their different clinical features of COVID-19. Moreover, they compared the results to previous studies from Europe, Asia, and the United States of America (USA).

The serum samples used in the study belonged to patients of distinct ethnic origins and disparate pathologic features, that is, asymptomatic, asymptomatic, and severe COVID-19.

Results

Study analysis confirmed that all identified IgG epitopes represent immunological epitopes. Previous studies from different continents similarly identified five and eight IgG epitopes in the N and S domains. Most IgG immunoreactive epitopes outside of the receptor-binding regions and terminal domains (RBD and NTD) of the SARS-CoV-2 S protein, which is the known hub of most SARS-mutants, are embedded CoV-2. Interestingly, many of these immune peptide epitopes are proven targets neutralizing antibodies, for example, S139/140, S165, S204, and S287/288. Similarly, the researchers found several IgM immunoreactive epitopes, possibly because they collected serum samples 10 to 12 days after the onset of symptoms. However, they did not find immunogenic epitopes in the SARS-CoV-2 E protein in this study, as in previous studies.

Moreover, the observed humoral responses to SARS-CoV-2 in subjects from Madagascar and Senegal were quite similar, with some differences due to different patient profiles at the time of sampling. The samples belonged to patients with SARS-CoV-2 infection in the early or late stages. Accordingly, asymptomatic patients had more IgM epitopes, and those with severe COVID-19 shifted toward IgG epitopes due to prolonged exposure to SARS-CoV-2. Based on IgG and IgM scores, even previous studies have shown a stronger immune response by critically ill COVID-19 patients than their asymptomatic or asymptomatic counterparts.

Another important observation the researchers made was that some critically ill patients no longer had a detectable SARS-CoV-2 load at the time of study sampling. Also, those with a higher score of neutralizing antibodies had fewer burden or viral load, suggesting that their humoral response may have eliminated the virus but could not help them survive. Patients from the severe group were older than the symptomatic and asymptomatic groups, and had a higher risk of contracting COVID-19.

conclusions

Overall, the analysis of the current study confirmed that the humoral immune response landscapes of African patients to SARS-CoV-2 were similar to those in other continents, indicating little or no effect of variation in the ethnicity and genetic background of these populations.

A set of 36 peptides nested within SARS-CoV-2 S and N structural proteins showed the highest reactivity with neutralizing antibodies. In particular, IgM, IgM/IgG, and IgG patients were assigned to nine, two, and 25 SARS-CoV-2 peptides, respectively. The specific immunoreactive IgG epitopes were similar to those described in the Asian, European and USA studies. These immune epitopes can aid in the development of new, effective vaccine candidates and rapid serological diagnostic assays.

The current study did not determine the role of T cells, which are a critical component of the humoral immune response to SARS-CoV-2. The lack of induction of an adequate T-cell response has resulted in death in some critically ill patients who developed an appropriate humoral response. It may be interesting for future studies to identify peptides that are recognized by T cells in these African patients.



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