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Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab.
Madelon, Natacha; Heikkilä, Nelli; Sabater Royo, Irène; Fontannaz, Paola; Breville, Gautier; Lauper, Kim; Goldstein, Rachel; Grifoni, Alba; Sette, Alessandro; Siegrist, Claire-Anne; Finckh, Axel; Lalive, Patrice H; Didierlaurent, Arnaud M; Eberhardt, Christiane S.
  • Madelon N; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Heikkilä N; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Sabater Royo I; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Fontannaz P; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Breville G; Division of Neurology, Department of Neurosciences, University Hospital of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Lauper K; Division of Rheumatology, Department of Medicine, University Hospital of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Goldstein R; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Grifoni A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, University of California, San Diego, La Jolla.
  • Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, University of California, San Diego, La Jolla.
  • Siegrist CA; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla.
  • Finckh A; Faculty of Medicine, Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  • Lalive PH; Division of General Pediatrics, Department of Woman, Child and Adolescent Medicine, Faculty of Medicine, University of Geneva, Center for Vaccinology, Geneva University Hospitals, Geneva, Switzerland.
  • Didierlaurent AM; Division of Rheumatology, Department of Medicine, University Hospital of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Eberhardt CS; Division of Neurology, Department of Neurosciences, University Hospital of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
JAMA Neurol ; 79(4): 399-404, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1711999
ABSTRACT
IMPORTANCE The 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

PARTICIPANTS:

In 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.

RESULTS:

Of 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, 73.6-114.5; 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 RELEVANCE In 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Multiple Sclerosis Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Humans / Male / Middle aged Language: English Journal: JAMA Neurol Year: 2022 Document Type: Article Affiliation country: Jamaneurol.2022.0245

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Multiple Sclerosis Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Vaccines / Variants Limits: Adult / Humans / Male / Middle aged Language: English Journal: JAMA Neurol Year: 2022 Document Type: Article Affiliation country: Jamaneurol.2022.0245