Patients with multiple sclerosis show robust T-cell responses to mRNA
COVID-19 vaccines

Date:
September 16, 2021
Source:
University of Pennsylvania School of Medicine
Summary:
New research shows that mRNA COVID-19 vaccines are effective
at inducing T-cell responses in multiple sclerosis patients who
receive B cell- depleting infusions even if their antibody responses
are diminished.



FULL STORY ==========================================================================
New research shows that Multiple Sclerosis (MS) patients undergoing
anti-CD20 (aCD20) treatment -- which depletes the B cells that contribute
to the MS attacks -- are able to mount robust T-cell responses to the
mRNA COVID-19 vaccines, despite having a muted antibody response to
the vaccines.


========================================================================== Because B cells are responsible for antibody production, patients'
ability to produce antibodies that prevent the virus from entering and infecting a person's cells is significantly muted when the B cells are
depleted with aCD20 treatment. But the same patients are nonetheless able
to mount very good responses of the second protective arm of their immune system, which uses T cells to eliminate cells once infected (thereby
preventing viral spread to other cells), according to new research from
the Perelman School of Medicine at the University of Pennsylvania in a
new paper published in Nature Medicine.

"The message from this study is clear -- it is worthwhile for patients
with MS receiving aCD20 treatment to get a COVID-19 vaccine, which will
prevent severe illness," said one of the senior authors E. John Wherry,
PhD, chair of Systems Pharmacology and Translational Therapeutics and
director of the Penn Institute for Immunology. "Based on this body of
evidence, we urge patients with MS receiving aCD20 treatment to get a
COVID-19 vaccine if they haven't already." The study measured both the antibody and T cell responses in 20 patients with MS who were undergoing
aCD20 treatment, compared to those in a group of healthy controls. None
of the participants in the study had prior clinical signs or symptoms of COVID-19. Researchers analyzed plasma and peripheral blood mononuclear
cell samples five times over the study period: prior to the first vaccine
dose, 10-12 days following the first vaccine dose, prior to the second
vaccine dose, 10-12 days following the second vaccine dose, and 25-30
days following the second vaccine dose.

All healthy control subjects generated both anti-spike and anti-receptor- binding domain (RBD) antibodies following the first dose of mRNA
vaccine, and the level of antibody increased further after the second
dose. However, in patients with MS, the antibody response was far more
varied. By 30 days after the second vaccine dose, 85% of participants
developed anti-spike antibodies, and 50% mounted anti-RBD responses. For
those subjects who did have detectable antibodies, the magnitude of
response was generally lower, and the response was delayed compared to
the control group.

The timing of a patient's last aCD20 infusion -- typically administered
every six months -- played a significant role in the immune response
mounted.

Patients with MS with higher percentages of circulating B cells prior
to the vaccine had more robust antibody responses to the vaccine.

"This data not only reveal that patients undergoing anti-CD20 infusions
are still able to mount important COVID-19 vaccine responses which are
likely to protect from severe illness, but also informs our clinical
practices in how we advise patients with MS and other autoimmune disorders
on such therapies," said another of the paper's senior authors Amit
Bar-Or, MD, FRCPC director of the Center for Neuroinflammation and
Experimental Therapeutics and chief of the Division of MS and Related Disorders. "For example, knowing that responses are weakest immediately following an anti-CD20 infusion, we can now advise patients to wait
a number of months after their therapy to get a COVID-19 vaccine."
Researchers found that patients who had undergone aCD20 treatments had subpopulations of T cells that responded similarly to vaccination as
healthy control subjects. Patients who underwent aCD20 therapy generated
robust CD4 and CD8 T cell responses to the COVID-19 vaccination. Further,
the CD8 T cell response was especially robust among the subgroup of
patients with MS who didn't generate RBD antibodies. This observation
reveals that even without circulating B cells, the COVID-19 vaccine
effectively primed patients' immune response to the virus.

"Often when determining if a patient mounted a proper response to an mRNA vaccine, we test for the presence of antibodies, but this method neglects
an entire arm of a person's immune response," said one of the lead authors Sokratis A. Apostolidis, MD, a fellow in the Department of Rheumatology.

"Measuring both antibodies and T-cell response gives us a more complete
picture of a patient's immune response, and reveals that patients who
can't generate antibodies as well as a healthy person are actually still protected by the COVID-19 vaccine." The researchers do note that due
to the limited antibody responses mounted by patients receiving aCD20 treatments, they might not be able to neutralize the virus as quickly
before it infects other cells, which could result in them being contagious carriers of the virus for a longer period of time.

This work was supported by grants from the NIH (AI105343, AI082630,
AI108545, AI155577, AI149680, AI152236, P30-AI0450080, R01 AI118694,
UC4 DK112217, T32 AR076951-01, T32 CA009140, U19AI082630, UM1 AI144288,
NMSS SI-2011-37160). This work was also supported by NIH contract
(Nr. 75N9301900065).

Funding was also provided by the Allen Institute for Immunology, Chen
Family Research Fund, the National Multiple Sclerosis Society-American
Brain Foundation Clinician Scientist Award, the Parker Institute for
Cancer Immunotherapy, the Penn Center for Research on Coronavirus and
Other Emerging Pathogens, the University of Pennsylvania Perelman School
of Medicine COVID Fund, the University of Pennsylvania Institute for
Immunology Glick COVID-19 research award, the University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund, a philanthropic
gift from Jeffrey Lurie, Joel Embiid, Josh Harris, and David Blitzer,
the Penn Center for Neuroinflammation and Experimental Therapeutics and
the Melissa and Paul Anderson Fund.

========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Sokratis A. Apostolidis, Mihir Kakara, Mark M. Painter, Rishi
R. Goel,
Divij Mathew, Kerry Lenzi, Ayman Rezk, Kristina R. Patterson,
Diego A.

Espinoza, Jessy C. Kadri, Daniel M. Markowitz, Clyde E. Markowitz,
Ina Mexhitaj, Dina Jacobs, Allison Babb, Michael R. Betts,
Eline T. Luning Prak, Daniela Weiskopf, Alba Grifoni, Kendall
A. Lundgreen, Sigrid Gouma, Alessandro Sette, Paul Bates, Scott
E. Hensley, Allison R. Greenplate, E.

John Wherry, Rui Li, Amit Bar-Or. Cellular and humoral immune
responses following SARS-CoV-2 mRNA vaccination in patients with
multiple sclerosis on anti-CD20 therapy. Nature Medicine, 2021;
DOI: 10.1038/s41591-021- 01507-2 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210916173434.htm

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