Abstract Details

Title An Observational Study on the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccination in Multiple Sclerosis and Other Autoimmune Neurological Disorders treated with Anti-CD20 Therapies

Topic Multiple Sclerosis

Presentation(s) S5 - COVID and MS Basic Science (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Background Anti-CD20 therapies attenuate humoral responses to vaccines. Their effect on T cell responses is unclear. We examined B and T cell responses with COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs).

Objective

To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination as it relates to spike binding IgG, neutralizing antibody titers, and T cell response.

Design/Methods Patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses before and after COVID-19 vaccination. Serum antibodies against the receptor-binding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD4 and CD8 T cell levels responses using activation-induced markers and INF-gamma release assay were measured at various time points including pre-vaccination, less than 12 weeks and greater than 12 weeks post initial vaccination series, and 4 and 12 weeks after 3rd “booster” vaccination.

Results

Twenty-five MS and AIND participants are enrolled as of 10/11/21 with projected enrollment complete by December 2021 (50-60 total). Preliminary results for 17 of these patients (mean age 44 years-old, 83% female, 16 Pfizer, 1 Moderna) demonstrated attenuated RBD IgG antibody responses. However, CD8 T cell response is robust compared to non-immunosuppressed, age-matched controls (n=22) less than 12 weeks after two dose series (p value = 0.0069) and sustained long-term (>12 weeks) in all eight anti-CD20 patients tested thus far. Additional analysis will include comparison between pre and post 3rd vaccination at 4- and 12-week timepoints.

Conclusions

Early results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA post initial series of vaccination but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.

Authors/Disclosures
Tyler L. Borko, BA (University of Colorado) PRESENTER	Mr. Borko has nothing to disclose.
Sean Selva	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Stefan Sillau	No disclosure on file
Daniel Pastula, MD, MHS, FAAN (University of Colorado, Department of Neurology)	Dr. Pastula has nothing to disclose.
Maite Sabalza (EUROIMMUN)	No disclosure on file
Iswariya Venkat (EUROIMMUN US)	No disclosure on file
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine)	Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $0-$499 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImCyse. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Enrique Alvarez, MD, PhD (University of Colorado)	Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Alvarez has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene/BMS. The institution of an immediate family member of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon.
Robert H. Gross, MD, FAAN (University of Colorado)	Dr. Gross has nothing to disclose.
Anna Shah, MD (University of Colorado, Neurology Dept)	The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. The institution of Dr. Shah has received research support from Genentech/Roche. Dr. Shah has received personal compensation in the range of $5,000-$9,999 for serving as a Educational Speaker with Rocky Mountain MS Center.
Ryan Kammeyer, MD (Childrens Hospital Colorado)	The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center.
Timothy L. Vollmer, MD, FAAN	The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics.
	No disclosure on file
John Corboy, MD, FAAN (U of Colorado School of Medicine)	Dr. Corboy has received personal compensation for serving as an employee of U of Coloado. Dr. Corboy has received personal compensation for serving as an employee of Rocky Mountain MS Center. Dr. Corboy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Mylan. Dr. Corboy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squib. Dr. Corboy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. Dr. Corboy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Neurological Association. Dr. Corboy has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Mylan. The institution of Dr. Corboy has received research support from MedDay. The institution of Dr. Corboy has received research support from Novartis. The institution of Dr. Corboy has received research support from NMSS. The institution of Dr. Corboy has received research support from PCORI. The institution of Dr. Corboy has received research support from EMD Serono.
Elena Hsieh (University of Colorado Denver)	No disclosure on file
Amanda L. Piquet, MD, FAAN (University of Colorado)	The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. The institution of Dr. Piquet has received personal compensation in the range of $0-$499 for serving as a Consultant for EMD Serono. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Joe Jones Law Firm. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. The institution of Dr. Piquet has received research support from Anokion. The institution of Dr. Piquet has received research support from UCB . The institution of Dr. Piquet has received research support from Foundation for Sarcoidosis. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Autoimmune Encephalitis Alliance (AEA) that is relevant to AAN interests or activities. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Stiff Person Syndrome Research Foundation (SPSRF) that is relevant to AAN interests or activities.