In a recent study published in Cell Reports Medicine, researchers evaluated the humoral and T lymphocyte immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) among mild coronavirus disease 2019 (COVID-19) convalescent patients in South Australia.
Background
Antibody responses and SARS-CoV-2 neutralization potential wane with time following SARS-CoV-2 infections and after vaccination with existing COVID-19 vaccines. SARS-CoV-2 VOCs possess several mutations in their spike (S) proteins which confer immune evasive properties to escape host immune responses. Therefore, the emergence of SARS-CoV-2 VOCs has increased the risk of convalescent patients and vaccine recipients to reinfections and has caused a hindrance in bringing the COVID-19 pandemic to an end.
About the study
In the present study, researchers assessed the humoral/antibody-mediated and T lymphocyte-mediated immunity among mild COVID-19 convalescents against SARS-CoV-2 VOCs after one year of infection with the ancestral (Wuhan-like) strain. The VOCs assessed were Alpha, Beta, Gamma, Delta, and Omicron.
The study cohort comprised 43 mild polymerase chain reaction (PCR)-confirmed COVID-19 convalescent patients.
Detailed assessments of immune responses against pseudotyped viruses, receptor-binding domain (RBD)-targeted B lymphocyte counts, and S- and non-S SARS-CoV-2 VOC-specific cluster of differentiation 4+ (CD4+) and CD8+ T lymphocyte immune responses, were undertaken. The neutralization of SARS-CoV-2 VOCs was assessed using neutralization assays. T lymphocytes were identified and quantified by activation-induced marker (AIM) assays using SARS-CoV-2 antigen peptide pools and flow cytometry analysis. The observations among the COVID-19 convalescents were compared to sex- and age-matched healthy individuals after six months and one year of infection.
In addition, the memory phenotype of SARS-CoV-2-specific CD4+ and CD8+ T lymphocytes was evaluated by measuring the expression of surface markers CD45RA and CCR7. Intracellular cytokine staining (ICS) of S-specific CD4+ and CD8+ T lymphocytes was performed to assess their functionality among the highly responding convalescents. Additionally. the frequency and functionality of -specific circulating T follicular helper cells (cTFH) were assessed.
Results
Despite the ancestral RBD-targeted antibody and circulating memory B lymphocyte titers being conserved among most individuals, serum neutralization against live Omicron was completely abrogated and substantially decreased for the other SARS-CoV-2 VOCs.
Similarly, the ancestral strain-specific memory T lymphocyte frequencies were maintained in more than half of the COVID-19 convalescents but the lymphocytic cytokine response to Omicron and Beta S epitopes was impaired. The relative frequencies of CD4+ and CD8+ T lymphocytes did not differ between the two time points (six months and one year) and between COVID-19 convalescents and healthy individuals.
RBD-targeted serological immunoglobulin G (IgG) titers declined for all VOC isotypes after six months and one year of infection with the area under the curve (AUC) titers declining from 73-200 to 28-82, from 67-218 to 0.8-4, and from 0-44 to 0.2-0.9 for IgG, IgG1 and IgG3, respectively. Above background levels of memory (CD27+) B lymphocytes expressing RBD-targeted IgG were observed among 89% of the convalescents (153 to 336 RBD-targeted lymphocytes/106 B lymphocytes) in comparison to healthy individuals (28 RBD-targeted /106 B lymphocytes). This was indicative of long-lasting (one year) humoral immune responses against SARS-CoV-2 among the COVID-19 convalescent patients.
After one year of infection, 64% and 44% of the serum samples of the COVID-19 convalescent patients yielded neutralization titers substantially above those of healthy controls against the ancestral S- and Alpha S-pseudotyped viruses. Neutralization titers for the live ancestral SARS-CoV-2 strain ranged between 16.8 and 40.8 with 51% of the convalescent patients demonstrating positive neutralizing activity.
Alpha neutralization titers ranged between 13 and 30. However, a remarkable decrease in live virus neutralization titers against Beta (0 to 2), Gamma (0.2 to 10), Delta (1.1 to 11), and Omicron (0.0 to 0.0) with only 5%, 12%, 16%, and 0% among the COVID-19 convalescents, respectively, demonstrating positive neutralization activity. This indicated that despite the increased prevalence of serum RBD-targeted antibodies, the existence of memory B lymphocytes, and SARS-CoV-2 neutralization by the COVID-19 convalescents, functional antibody-mediated/humoral immunity against SARS-CoV-2 VOCs substantially decreased one year after infection and were entirely abolished for Omicron.
In the phenotype analysis, between six months and 12 months of infection, the frequency of S-specific CD4+ T lymphocytes was substantially decreased in all memory compartments, central memory T lymphocytes (from 0.3-0.7 to 0.2-0.4), effector memory T lymphocytes (from 1-2 to 0.8-1.5) and terminal effector T lymphocytes (from 0.7-1.2 to 0.3-0.9). A similar trend was observed for memory subsets of non-S CD4+ T lymphocytes.
After one year of infection, the frequency of S-specific cTFH among the mild COVID-19 convalescent patients and healthy individuals did not differ significantly. Likewise, the frequencies of cTFH lymphocytes expressing cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and cytotoxic molecules such as granzyme B and perforins, were comparable among the two groups.
Conclusion
Overall, the study findings showed that Omicron was more immune evasive than other SARS-CoV-2 variants. The results highlighted the impairment in humoral and S-specific T lymphocyte immune responses post-infection among mild COVID-19 convalescent patients due to antigenic variability of the variants of concern.
- Lim, C., Beard, M.R, Weiskopf, D., Sette, A., Turville, S.G, Bull, R.A., Barry, S.C., Grubor-Bauk., B. (2022). SARS-CoV-2 Omicron variant escapes neutralising antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents., Cell Reports Medicine. doi: https://doi.org/10.1016/j.xcrm.2022.100651 https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00183-5
Posted in: Medical Science News | Medical Research News | Disease/Infection News
Tags: Antibodies, Antibody, Antigen, B Lymphocyte, CD4, Cell, Coronavirus, Coronavirus Disease COVID-19, covid-19, CT, Cytokine, Cytokines, Cytometry, Flow Cytometry, Frequency, immunity, Immunoglobulin, Interferon, Interferon-gamma, Interleukin, Interleukin-2, Intracellular, Lymphocyte, Medicine, Necrosis, Omicron, Pandemic, Phenotype, Polymerase, Polymerase Chain Reaction, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, T Lymphocyte, Tumor, Tumor Necrosis Factor, Vaccine, Virus
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Pooja Toshniwal Paharia
Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.
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