Is Protection Conferred by Third COVID-19 Vaccine in Patients With MS?

Deborah L. Ungerleider, MD, for Medscape

February 08, 2022

The study covered in this summary was published in as a preprint and has not yet been peer reviewed.

Key Takeaways

  • There was only a minimal increase in antibody titers and seroconversion seen after the third SARS-CoV-2 mRNA vaccine in patients with multiple sclerosis who had been treated with the anti-CD20 therapy, ocrelizumab, as compared with healthy controls.

  • The time intervals between the ocrelizumab dose and the third vaccine dose did not correlate with antibody levels.

Why This Matters

  • Patients with multiple sclerosis who are being treated with anti-CD20 are at high risk of severe complications from SARS-CoV-2 infection; therefore, it is important to have a vaccine that confers lasting protective immunity to this virus.

  • The findings from this study point to the need for a way to increase B cells in these patients, possibly by using monoclonal antibodies or other ways of repleting the B cells prior to SARS-CoV-2 vaccination.

Study Design

  • This was a prospective, longitudinal, observational study that included patients 18 years of age or older with multiple sclerosis who were being treated with anti-CD20 (ocrelizumab).

  • The patients were seen at one of two Danish clinics or the Multiple Sclerosis and Neuroinflammation Center at the University of California, San Francisco.

  • The patients had already received two doses of the SARS-CoV-2 mRNA vaccine and were eligible for a third (booster) vaccine.

  • Blood samples to measure the IgG antibody levels of the SARS-CoV-2 spike receptor binding domain were taken before and after all three doses of the vaccine.

  • Measurements of B cells, T cells, and spike-specific T-cell responses were also done.

Key Results

  • Detectable antibodies were found in 14% of the participants 0–7 days before the second vaccine; this increased to 37.7% by 2–4 weeks after that vaccine. It then decreased to 24.0% at 0–7 days before the third vaccine; 33.3% of the patients who had antibodies at the 2- to 4-week point had no antibodies by 0–7 days before the third vaccine.

  • The antibodies were significantly lower at the 0- to 7-day point than they were at the 2- to 4-week post–second vaccine point (P = .0020).

  • Following the third vaccine, 33.3% of the participants had positive antibodies, with 25.6% of participants having detectable antibodies at both 2–4 weeks after the second vaccine and 2–4 weeks after the third vaccine. Of the participants who did not have detectable antibodies prior to the third dose, 13.2% had detectable levels after the third vaccine.

  • Regarding the levels of antibodies needed for protection against infection, 7.4% of the participants had low levels that would confer less than 50% protection; 24% had intermediate levels, giving above 50% protection; and 1.8% (only one patient) had high levels, giving more than 80% protection.

  • The levels of B cells and T cells were not different between the patients who had detectable antibodies (seropositive) and those who did not (seronegative) 0–7 days before the third booster.

  • The frequencies of the spike-reactive T cells increased from before the first vaccine compared with after the second vaccine; however, there was only a slight increase after the third vaccine.

  • The median age of the participants did not differ between the seropositive and seronegative individuals (P = .2254).

  • The interval between the time a patient received their last dose of ocrelizumab and their third vaccine dose did not correlate with their antibody levels (r2 = 0.04008, P = .44).

  • Additionally, the interval between the second and third vaccine doses did not correlate with the patient's antibody levels (r2 = 0.00097, P = .90).


  • The time frame used was short; therefore, there were missing samples at the last two blood collections (0–7 days before the third booster vaccination and 2–4 weeks after the third booster vaccination).

  • The levels of responses used as cutoffs were based on the previous variants of SARS-CoV-2; they did not include the Delta or Omicron variants.


  • This study was conducted with fundings from the Danish Neurological Society, Lundbeck, and Roche.

  • Joseph J. Sabatino, Jr, has received research support from Novartis.

  • Riley Bove has received research support from Biogen, Roche Genentech, and Novartis; has received personal consulting fees from Alexion, Biogen, EMD Serono, Novartis, Roche Genentech, and Sanofi Genentech; and is funded by a Harry Weaver Award from the National Multiple Sclerosis Society and the National Institutes of Health.

  • Scott S. Zamvil has received consulting honoraria from Alexion, Biogen-Idec, EMD-Serono, Genzyme, Novartis, Roche/Genentech, and Teva Pharmaceuticals, Inc, and has served on data safety monitoring boards for Lilly, BioMS, Teva, and Therapeutics.

  • Tobias Sejbaek has received travel grants from Biogen, Merck, Novartis, and Roche; has received research grants from Biogen; and has served on advisory boards for Biogen, Merck, and Novartis.

  • Hamza Mahmood Bajwa, Frederik Novak, Anna Christine Nilsson, Keld-Erik Byg, Isik S. Johansen, Christian Nielsen, Dorte K. Holm, A. B. Jacobsen, Kristen Mittl, and William Rowles have disclosed no relevant financial relationships.

This is a summary of a preprint research study, "Persistently Reduced Humoral and Cellular Immune Response Following Third SARS-CoV-2 mRNA Vaccination in Anti-CD20-Treated Multiple Sclerosis Patients," written by Hamza Mahmood Bajwa and colleagues from the Department of Neurology, Hospital Southwest Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark, and the Department of Regional Health Research, University of Southern Denmark, Odense, Denmark, on medRxiv, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on


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