Segato Irene, Mele Dalila, Forlani Greta, Dalla Gasperina Daniela, Mondelli Mario U, Varchetta Stefania
PhD National Programme in One Health Approaches to Infectious Diseases and Life Science Research, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy.
Division of Microbiology and Virology, Department of Diagnostic Services, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
Vaccines (Basel). 2024 Dec 23;12(12):1451. doi: 10.3390/vaccines12121451.
BACKGROUND/OBJECTIVES: New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA.2.86 and JN.1 variants, particularly in elderly individuals.
We evaluated T cell and total IgG responses against the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 strain, as well as BA.2.86 and JN.1 omicron subvariants, in two groups of subjects. One group consisted of SARS-CoV-2-exposed elderly individuals who were fully vaccinated with the BNT162B2 mRNA vaccine, with a booster dose of the updated 2023-2024 COVID-19 vaccine (XBB.1.5) at least 15 days after receiving a booster dose of the updated 2023-2024 COVID-19 vaccine. The second group consisted of healthcare workers who were unexposed to SARS-CoV-2 one month after the booster dose of the first-generation BNT162b2 mRNA vaccine. T cell activation-induced markers (AIM) and IFN-γ secretion were evaluated by flow cytometry and ELISpot assays, respectively.
Elderly subjects showed reduced IgG levels against JN.1 compared with the ancestral strain. BA.2.86 stimulation resulted in lower IFN-γ levels in the elderly versus the COVID-19-naïve group. AIM analysis showed that among T cells, CD4+ were the most responsive, with a reduced proportion of JN.1-reactive CD4+ T cells compared with the ancestral strain in the SARS-CoV-2-unexposed group. Despite receiving the updated booster, the elderly group showed reduced CD4+ T cell reactivity to BA.2.86.
The XBB.1.5-containing vaccine induced lower CD4+ T cell responses against BA.2.86 in the elderly. CD4+ T cells from BNT16b2-vaccinated, COVID-19-naïve subjects recognized ancestral and BA.2.86 RBD strains while showing reduced responses to JN.1. These results emphasize the need for tailored vaccine strategies for emerging variants, particularly in vulnerable populations.
背景/目的：新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体不断出现，因此评估疫苗诱导的免疫保护效果至关重要。关于T细胞对BA.2.86和JN.1变体的反应，尤其是在老年个体中的信息有限。
我们评估了两组受试者针对原始SARS-CoV-2毒株以及BA.2.86和JN.1奥密克戎亚变体的受体结合域（RBD）的T细胞和总IgG反应。一组由接触过SARS-CoV-2的老年个体组成，他们已用BNT162B2 mRNA疫苗全程接种，并在接种2023 - 2024年更新的新冠疫苗（XBB.1.5）加强剂量至少15天后，又接种了该疫苗的加强针。第二组由在第一代BNT162b2 mRNA疫苗加强剂量接种一个月后未接触过SARS-CoV-2的医护人员组成。分别通过流式细胞术和酶联免疫斑点试验评估T细胞活化诱导标志物（AIM）和干扰素-γ分泌。
与原始毒株相比，老年受试者针对JN.1的IgG水平降低。与未感染过新冠病毒的组相比，BA.2.86刺激导致老年组的干扰素-γ水平较低。AIM分析表明，在T细胞中，CD4 +细胞反应性最强，在未接触过SARS-CoV-2的组中，与原始毒株相比，对JN.1有反应的CD4 + T细胞比例降低。尽管接种了更新的加强针，但老年组对BA.2.86的CD4 + T细胞反应性仍降低。
含XBB.1.5的疫苗在老年个体中诱导的针对BA.2.86的CD4 + T细胞反应较低。接种BNT16b2疫苗且未感染过新冠病毒的受试者的CD4 + T细胞能够识别原始和BA.2.86的RBD毒株，但对JN.1的反应降低。这些结果强调了针对新出现的变体制定个性化疫苗策略的必要性，特别是在脆弱人群中。
Zotero 插件
