Infectious Disease Unit, Department of System Medicine, Tor Vergata University and Hospital, Rome, Italy.
Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, Tor Vergata University and Hospital, Rome, Italy.
Front Immunol. 2022 Jan 17;12:796482. doi: 10.3389/fimmu.2021.796482. eCollection 2021.
Vaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).
PwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.
Thirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.
The evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.
为了遏制严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的传播而开展的疫苗接种运动，引发了人们对多发性硬化症（MS）患者等特殊人群中疫苗免疫原性的关注，这些患者正在接受高效疾病修正治疗（DMTs）。虽然人们已经很好地了解了 SARS-CoV-2 mRNA 疫苗在普通人群和 MS 患者中的体液反应，但对于细胞介导反应在预防 SARS-CoV-2 感染和严重 2019 年冠状病毒病（COVID-19）方面的保护作用，我们知之甚少。
我们招募了接受两剂 mRNABNT162b2（Comirnaty）疫苗接种的接受奥瑞珠单抗、芬戈利莫德或那他珠单抗治疗的 MS 患者。在接种疫苗至少 1 个月且不超过疫苗第二次接种后 4 个月时，评估抗刺突（S）和抗核蛋白（N）抗体滴度、S 和 N 肽库刺激后产生的 IFN-γ以及外周血淋巴细胞绝对计数。同时还招募了一组年龄和性别匹配的健康供体（HD）作为参考组。使用 GraphPad Prism 8.2.1 进行统计分析。
共纳入 30 名 MS 患者和 9 名 HD。所有患者的抗 N 抗体检测均为阴性，也未报告过 COVID-19 相关症状。对 MS 患者的外周血淋巴细胞计数进行评估，结果显示：（i）奥瑞珠单抗治疗的 MS 患者外周血 B 淋巴细胞减少；（ii）接受芬戈利莫德治疗的 MS 患者外周血 B 细胞和 T 细胞绝对计数减少；（iii）接受那他珠单抗治疗的 MS 患者外周血 B 细胞和 T 细胞绝对计数正常，但循环 CD16+CD56+NK 细胞增加。在 MS 患者中，共确定了三种免疫反应模式。奥瑞珠单抗治疗的患者缺乏或减少了抗 S 抗体，而 T 细胞反应正常。接受芬戈利莫德治疗的患者抗 S 滴度和 T 细胞介导的反应均受损。接受那他珠单抗治疗的患者，抗 S 滴度和 T 细胞反应均存在且与 HD 中的观察结果相当。
在 DMT 治疗的 MS 患者中评估 T 细胞反应、抗 S 滴度和外周血淋巴细胞绝对计数，可以帮助更好地描述 SARS-CoV-2 疫苗接种后的免疫反应。在 MS 患者的纵向队列中评估 T 细胞反应有助于阐明其在预防 SARS-CoV-2 感染和严重 COVID-19 方面的保护作用。DMT 治疗与 SARS-CoV-2 疫苗免疫反应之间的相关性，有助于更好地评估 MS 患者的疫苗接种策略。
