DataSheet_1_Differential cellular and humoral immune responses in immunocompromised individuals following multiple SARS-CoV-2 vaccinations.pdf

IntroductionThe heterogeneity of the immunocompromised population means some individuals may exhibit variable, weak or reduced vaccine-induced immune responses, leaving them poorly protected from COVID-19 disease despite receiving multiple SARS-CoV-2 vaccinations. There is conflicting data on the immunogenicity elicited by multiple vaccinations in immunocompromised groups. The aim of this study was to measure both humoral and cellular vaccine-induced immunity in several immunocompromised cohorts and to compare them to immunocompetent controls.
MethodsCytokine release in peptide-stimulated whole blood, and neutralising antibody and baseline SARS-CoV-2 spike-specific IgG levels in plasma were measured in rheumatology patients (n=29), renal transplant recipients (n=46), people living with HIV (PLWH) (n=27) and immunocompetent participants (n=64) post third or fourth vaccination from just one blood sample. Cytokines were measured by ELISA and multiplex array. Neutralising antibody levels in plasma were determined by a 50% neutralising antibody titre assay and SARS-CoV-2 spike specific IgG levels were quantified by ELISA.
ResultsIn infection negative donors, IFN-γ, IL-2 and neutralising antibody levels were significantly reduced in rheumatology patients (p=0.0014, p=0.0415, p=0.0319, respectively) and renal transplant recipients (p<0.0001, p=0.0005, p<0.0001, respectively) compared to immunocompetent controls, with IgG antibody responses similarly affected. Conversely, cellular and humoral immune responses were not impaired in PLWH, or between individuals from all groups with previous SARS-CoV-2 infections.
DiscussionThese results suggest that specific subgroups within immunocompromised cohorts could benefit from distinct, personalised immunisation or treatment strategies. Identification of vaccine non-responders could be critical to protect those most at risk.

引言 免疫功能低下（immunocompromised）人群具有异质性，部分个体可能表现出可变、微弱或减弱的疫苗诱导免疫应答，即便接种多剂新型冠状病毒（SARS-CoV-2）疫苗，仍难以获得针对新型冠状病毒肺炎（COVID-19）的有效保护。目前针对免疫功能低下人群多次接种疫苗后的免疫原性数据存在分歧。本研究旨在对多个免疫功能低下队列的疫苗诱导体液免疫与细胞免疫水平进行检测，并与免疫功能正常对照组进行比较。
方法 本研究仅通过单份血液样本，对29名风湿病患者（n=29）、46名肾移植受者（n=46）、27名人类免疫缺陷病毒感染者（PLWH）（n=27）以及64名免疫功能正常参与者（n=64）在完成第三剂或第四剂疫苗接种后的相关指标进行检测：包括肽刺激全血的细胞因子释放水平，血浆中的中和抗体水平以及基线新型冠状病毒刺突蛋白特异性IgG水平。细胞因子通过酶联免疫吸附试验（ELISA）与多重阵列检测进行定量；血浆中和抗体水平通过50%中和抗体滴度测定法确定；新型冠状病毒刺突蛋白特异性IgG水平则通过ELISA进行定量。
结果 在未感染过新型冠状病毒的受试者中，与免疫功能正常对照组相比，风湿病患者的γ干扰素（IFN-γ）、白细胞介素2（IL-2）以及中和抗体水平均显著降低（分别对应P=0.0014、P=0.0415、P=0.0319），肾移植受者的上述指标同样显著降低（分别对应P<0.0001、P=0.0005、P<0.0001），IgG抗体应答也受到类似影响。与之相反，人类免疫缺陷病毒感染者的细胞与体液免疫功能未受损伤，且所有既往感染过新型冠状病毒的受试者均未出现免疫应答受损情况。
讨论 本研究结果提示，免疫功能低下队列中的特定亚组或许可从差异化的个性化免疫接种或治疗策略中获益。识别疫苗无应答者，对于保护最高危人群而言至关重要。