Time-dependent contraction of the SARS-CoV-2-specific T-cell responses in convalescent individuals

Edgar Ruz Fernandes; Juliana de Souza Apostolico; Lucas Cauê Jacintho; Maria Lucia Carnevale Marin; Roberto Carlos Vieira da Silva Júnior; Hélcio Rodrigues; Keity Souza Santos; Verônica Coelho; Silvia Beatriz Boscardin; Jorge Kalil; Edecio Cunha-Neto; Daniela Santoro Rosa

doi:10.1016/j.jacig.2022.05.002

Time-dependent contraction of the SARS-CoV-2-specific T-cell responses in convalescent individuals

J Allergy Clin Immunol Glob. 2022 Aug;1(3):112-121. doi: 10.1016/j.jacig.2022.05.002. Epub 2022 Jun 6.

Authors

Edgar Ruz Fernandes¹, Juliana de Souza Apostolico^{1

2}, Lucas Cauê Jacintho³, Maria Lucia Carnevale Marin^{3

4}, Roberto Carlos Vieira da Silva Júnior^{3

4}, Hélcio Rodrigues³, Keity Souza Santos^{2

4

5}, Verônica Coelho^{2

4

5}, Silvia Beatriz Boscardin^{2

6}, Jorge Kalil^{2

3}, Edecio Cunha-Neto^{2

3

5}, Daniela Santoro Rosa^{1

2}

Affiliations

¹ Departamento de Microbiologia, Imunologia e Parasitologia da Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
² Instituto de Investigação em Imunologia (iii)-INCT, São Paulo, Brazil.
³ Laboratório de Imunologia, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
⁴ Laboratório de Imunologia Clínica e Alergia (LIM-60), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
⁵ Laboratório de Investigação Médica (LIM-19), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
⁶ Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Abstract

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation.

Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ-producing cells to in silico-predicted peptides in samples from SARS-CoV-2 convalescent individuals.

Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4⁺ and CD8⁺ T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity.

Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides.

Conclusion: Our data are evidence that in silico-predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time.

Keywords: AIM, Activation-induced marker; COVID-19; COVID-19, Coronavirus disease 2019; DMSO, Dimethyl sulfoxide; ELISPOT, Enzyme-linked immunospot; OR, Odds ratio; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus-2; SFU, Spot-forming unit; T lymphocyte; VOC, Variant of concern; adaptive immunity.