Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab

Abstract

IMPORTANCEThe SARS-CoV-2 variant B.1.1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses.OBJECTIVE To determine T-cell responses to the Omicron spike protein in anti-CD20-treated patients with multiple sclerosis (MS) before and after a third messenger RNA COVID-19 vaccination. DESIGN, SETTING, AND PARTICIPANTSIn this prospective cohort study conducted from March 2021 to November 2021 at the University Hospital Geneva, adults with MS receiving anti-CD20 treatment (ocrelizumab) were identified by their treating neurologists and enrolled in the study. A total of 20 patients received their third dose of messenger RNA COVID-19 vaccine and were included in this analysis.INTERVENTIONS Blood sampling before and 1 month after the third vaccine dose.MAIN OUTCOMES AND MEASURES Quantification of CD4 and CD8 (cytotoxic) T cells specific for the SARS-CoV-2 spike proteins of the vaccine strain as well as the Delta and Omicron variants, comparing frequencies before and after the third vaccine dose. RESULTSOf 20 included patients, 11 (55%) were male, and the median (IQR) age was 45.8 (37.8-53.3) years. Spike-specific CD4 and CD8 T-cell memory against all variants were maintained in 9 to 12 patients 6 months after their second vaccination, albeit at lower median frequencies against the Delta and Omicron variants compared with the vaccine strain (CD8 T cells: Delta, 83.0%; 95% CI, Omicron, 78.9%; 95% CI, 59.4-100.0; CD4 T cells: Delta, 72.2%; 95% CI, 67.4-90.5; Omicron, 62.5%; 95% CI, 51.0-89.0). A third dose enhanced the number of responders to all variants (11 to 15 patients) and significantly increased CD8 T-cell responses, but the frequencies of Omicron-specific CD8 T cells remained 71.1% (95% CI, 41.6-96.2) of the responses specific to the vaccine strain. CONCLUSIONS AND RELEVANCEIn this cohort study of patients with MS treated with ocrelizumab, there were robust T-cell responses recognizing spike proteins from the Delta and Omicron variants, suggesting that COVID-19 vaccination in patients taking B-cell-depleting drugs may protect them against serious complications from COVID-19 infection. T-cell response rates increased after the third dose, demonstrating the importance of a booster dose for this population.

Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis on Ocrelizumab or Fingolimod

“…We established that a third vaccination induces a recall of SARS-CoV-2 T cells in OCR-treated patients but does not further increase circulating SARS-CoV-2 T-cell numbers compared with after the second vaccination. This is in agreement with recent studies describing a T-cell recall after the third vaccination, 2 , 3 which was similar compared with the second vaccination for both OCR-treated patients and healthy controls. 2 T-cell responses induced by the vaccine have been demonstrated to be only minorly compromised to variants of concerns, including Omicron, both in healthy controls 4 as in OCR-treated patients.…”

“… 2 T-cell responses induced by the vaccine have been demonstrated to be only minorly compromised to variants of concerns, including Omicron, both in healthy controls 4 as in OCR-treated patients. 3 …”

Booster COVID-19 Vaccines for Immune-Mediated Inflammatory Disease Patients: A Systematic Review and Meta-Analysis of Efficacy and Safety

“…The screening process is illustrated in the PRISMA flowchart in Figure 1 . Of these studies, there were 12 observational studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], one randomised-controlled trial [ 33 ], and four case series [ 34 , 35 , 36 , 37 ]. The key trial characteristics of each included study are reported in Table 1 , with a comparison of the characteristics of the studies included in the meta-analysis in Table S2 .…”

Safety, Adherence and Persistence in a Real-World Cohort of German MS Patients Newly Treated With Ocrelizumab: First Insights From the CONFIDENCE Study

“…In the context of COVID-19, whether antibody production is the appropriate or sole immune correlate of protection is currently unknown and the role of T or B cell-mediated immunity for effective clinical protection requires additional investigations. Available data report impaired humoral response to SARS-CoV-2 infection or vaccines in ocrelizumab treated patients, but induced robust cellular response ( 28 – 35 ), significantly boosted after a third vaccine dose ( 36 ), or preserved against SARS-CoV-2 Delta or Omicron variants ( 37 ). Despite the impaired humoral immune response to SARS-CoV2 infection or vaccine, no known correlation with clinical severity has been established, as compensatory cellular-mediated immune response could provide protection against serious complications from COVID-19 infection.…”