Institut d'Immunologie, U1286 - INFINITE - Institute for Translational Research in Inflammation Inserm Univ. Lille, Centre Hospitalier Universitaire (CHU) Lille, Lille, France.
Pôle de Gériatrie, Hôpital Gériatrique Les Bateliers, Centre Hospitalier Universitaire (CHU) de Lille, Université de Lille, Lille, France.
Front Immunol. 2021 Nov 16;12:778679. doi: 10.3389/fimmu.2021.778679. eCollection 2021.
Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4- and CD8-specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older ( = 54) compared with the COVID-19-naive younger adults ( = 121). Notably, older participants' neutralizing antibodies were 10 times lower than the younger's antibody titers ( < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ and IFNγIL-2TNFα cells among specific CD4 T cells, and the frequency of specific CD8 T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults ( < 0.0001 and = 0.0018, respectively). However, COVID-19-recovered older participants ( = 51) had greater antibody and T-cell responses, including IFNγ and IFNγIL-2TNFα-specific CD4 T cells ( < 0.0001), as well as TNFα-specific CD8 T cells ( < 0.001), than COVID-19-naive older adults. We also observed that "inflammageing" and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4 and CD8 T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people.
长期护理机构（LTCF）的老年居民表现出细胞和体液免疫的生理改变，这影响了疫苗的反应。初步报告表明，对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的早期接种后抗体反应较低。本研究的目的是关注特定的 T 细胞反应。我们通过酶联免疫斑点法（ELISpot）量化了 S1 特异性 IgG、中和抗体滴度、总特异性 IFNγ 分泌 T 细胞，并通过流式细胞术量化了 CD4 和 CD8 特异性 T 细胞的功能，这些都是在接受了两剂 BNT162b2 疫苗后，分别在有和没有既往 COVID-19 感染的年轻人和老年人（此后分别称为 COVID-19 康复者和 COVID-19 未感染者）中进行的。在 COVID-19 未感染者的老年人中，在基线时收集了虚弱、营养和免疫衰老参数。我们分析了 129 名年轻成年人（中位年龄 44.0 岁）和 105 名居住在 LTCF 的老年人（中位年龄 86.5 岁）的免疫反应，这些人在第一次注射后 3 个月。与 COVID-19 未感染者的年轻人（n=121）相比，COVID-19 未感染者的老年人（n=54）的体液和细胞记忆反应明显受损。值得注意的是，老年参与者的中和抗体比年轻参与者的抗体滴度低 10 倍（<0.0001），LTCF 居民的功能性 T 细胞反应也受损：特定 CD4 T 细胞中 IFNγ 和 IFNγIL-2TNFα 细胞的频率，以及特定 CD8 T 细胞的频率在 COVID-19 未感染者的老年人中均低于 COVID-19 未感染者的年轻人（<0.0001 和=0.0018，分别）。然而，COVID-19 康复的老年人（n=51）的抗体和 T 细胞反应更大，包括 IFNγ 和 IFNγIL-2TNFα 特异性 CD4 T 细胞（<0.0001），以及 TNFα 特异性 CD8 T 细胞（<0.001），均高于 COVID-19 未感染者的老年人。我们还观察到，“炎症衰老”，特别是 TNFα 的高血浆水平与老年人的抗体反应不良有关。总之，我们的研究结果表明，COVID-19 未感染者的老年人的计数较低，特定的 CD4 和 CD8 T 细胞受损，此外，抗体反应也受损，需要进行专门研究来评估 SARS-CoV-2 mRNA 疫苗的效率，就像在其他免疫功能低下的人群中一样。我们的研究还表明，尽管免疫功能存在生理性改变，但疫苗接种在 COVID-19 康复的老年人中高度有效地增强了先前的自然记忆反应。
