Fernandes Edgar Ruz, de Souza Apostolico Juliana, Jacintho Lucas Cauê, Carnevale Marin Maria Lucia, Vieira da Silva Júnior Roberto Carlos, Rodrigues Hélcio, Santos Keity Souza, Coelho Verônica, Boscardin Silvia Beatriz, Kalil Jorge, Cunha-Neto Edecio, Rosa Daniela Santoro
Departamento de Microbiologia, Imunologia e Parasitologia da Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil.
Instituto de Investigação em Imunologia (iii)-INCT, São Paulo, Brazil.
J Allergy Clin Immunol Glob. 2022 Aug;1(3):112-121. doi: 10.1016/j.jacig.2022.05.002. Epub 2022 Jun 6.
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.
We aimed to characterize the specific T-cell response on the basis of the recall of IFN-γ-producing cells to -predicted peptides in samples from SARS-CoV-2 convalescent individuals.
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 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.
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.
Our data are evidence that -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.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染中的适应性免疫对疾病控制起决定性作用。T细胞的延迟激活与2019冠状病毒病(COVID-19)的更差预后相关。尽管康复个体表现出强大的T细胞免疫,但迄今为止,对SARS-CoV-2的长期免疫仍在研究中。
我们旨在根据对SARS-CoV-2康复个体样本中产生干扰素-γ的细胞对预测肽的回忆反应来表征特异性T细胞反应。
筛选SARS-CoV-2基因组序列,从而鉴定出预计可被CD4和CD8 T细胞识别的特异性和多反应性肽。接下来,我们从参与者的外周血单核细胞(PBMC)样本中进行特异性T细胞的回忆反应。根据队列的临床特征和HLA多样性对结果进行分析。
我们的结果表明参与者之间T细胞反应性存在异质性。与表现出轻度症状的患者相比,住院患者的反应程度明显更高。此外,男性和老年患者产生干扰素-γ的细胞数量较少。对180天后采集的样本进行分析发现,特异性循环产生干扰素-γ的T细胞数量减少,表明对病毒肽的免疫力下降。
我们的数据证明,预测肽能被康复个体的T细胞高度识别,这为疫苗设计提供了可能的应用方向。然而,感染180天后特异性T细胞数量减少,这可能与随着时间推移对再次感染的保护作用降低有关。