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mRNA 疫苗接种后对关注的 SARS-CoV-2 变异株的 T 细胞反应降低与 HIV 感染者突破性感染的风险。

Lower T cell response against SARS-CoV-2 variants of concern after mRNA vaccine and risk of breakthrough infections in people with HIV.

机构信息

Department of Infectious Diseases, CIBERINFEC (Centro de Investigacion en Red en Enfermedades Infecciosas, Biomedical Research Center Network in Infectious Diseases).

Laboratory of Immunovirology, Hospital Universitario Ramón y Cajal, Madrid, Spain.

出版信息

AIDS. 2023 May 1;37(6):877-882. doi: 10.1097/QAD.0000000000003504. Epub 2023 Feb 7.

DOI:10.1097/QAD.0000000000003504
PMID:36779501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10089930/
Abstract

OBJECTIVES

We evaluated T-cell immune responses against SARS-CoV-2 variants of concern (VOC) after vaccination in people with HIV (PWH), and their impact on the incidence of disease.

METHODS

A prospective cohort study. Peripheral blood mononuclear cells (PBMCs) were collected a median of 53 days after second dose of mRNA vaccine. Humoral response and T cell responses against the spike (S) glycoprotein of wild-type SARS-CoV-2 (ancestral Wuhan variant) and mutated S-protein regions found in the Delta and Omicron variants were assessed by flow cytometry analysis.

RESULTS

In 142 PWH without preceding SARS-CoV-2 infection, bivariate correlations showed a close association between T-cell responses to the different variants. However, despite at least 70% of PWH having a cellular immune response to any variant, CD4 + and CD8 + T cell responses against VOC were lower in frequency and magnitude (-3% and -20% for Delta, -33% and -28% for Omicron variant) compared with that observed against the Wuhan strain. A higher magnitude of SARS-CoV-2 spike-specific CD8 + T cell responses against all the variants was observed in those PWH with greater immune reconstitution. Notably, 27 symptomatic breakthrough infections (19%) in the setting of Delta and Omicron transmission were observed during follow-up, associated with a significant lower humoral and T-cell response to ancestral strain and VOC. On the contrary, only one PWH with COVID-19 (4%) required hospitalization.

CONCLUSION

A blunted T-cell response against Delta and Omicron variant is observed in PWH who received two doses of mRNA vaccine. This lower immune response is associated with breakthrough SARS-CoV-2 infections.

摘要

目的

我们评估了 HIV 感染者(PWH)接种疫苗后针对 SARS-CoV-2 关注变异株(VOC)的 T 细胞免疫反应及其对疾病发生率的影响。

方法

前瞻性队列研究。在 mRNA 疫苗接种后中位数 53 天采集外周血单核细胞(PBMC)。通过流式细胞术分析评估针对野生型 SARS-CoV-2(原始武汉株)和 Delta 和奥密克戎变异株中发现的突变 S 蛋白区域的 Spike(S)糖蛋白的体液反应和 T 细胞反应。

结果

在 142 名未感染过 SARS-CoV-2 的 PWH 中,双变量相关性表明 T 细胞对不同变异株的反应密切相关。然而,尽管至少有 70%的 PWH 对任何变异株均有细胞免疫反应,但针对 VOC 的 CD4+和 CD8+T 细胞反应的频率和幅度均较低(与武汉株相比,Delta 变异株分别降低 3%和 20%,Omicron 变异株分别降低 33%和 28%)。在免疫重建较好的 PWH 中,针对所有变异株的 SARS-CoV-2 刺突特异性 CD8+T 细胞反应幅度更大。值得注意的是,在 Delta 和 Omicron 传播期间,观察到 27 例(19%)有症状的突破性感染,这与针对原始株和 VOC 的体液和 T 细胞反应显著降低有关。相反,仅有 1 例 COVID-19(4%)的 PWH 需要住院治疗。

结论

在接受两剂 mRNA 疫苗接种的 PWH 中观察到针对 Delta 和 Omicron 变异株的 T 细胞反应减弱。这种较低的免疫反应与突破性 SARS-CoV-2 感染有关。

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