Abstract Details

Title Temporal Trends in Humoral and Cellular Immune Responses to SARS-CoV-2 mRNA Vaccines Among Multiple Sclerosis Patients Treated With Natalizumab, Ocrelizumab or Fumarates

Topic Multiple Sclerosis

Presentation(s) P14 - Poster Session 14 (11:45 AM-12:45 PM)

Poster/Presentation
Number 12-006

Objective To examine the temporal trends of humoral and cell-mediated immune responses to SARS-CoV-2 mRNA vaccines among multiple sclerosis (MS) patients on different immunomodulatory therapies.

Background The impact of various MS medications on the immune responses to SARS-CoV-2 vaccine is of acute interest to patients and clinicians.

Design/Methods

22 MS patients treated with ocrelizumab (OCR, n=9), natalizumab (NTZ, n=8), fumarates (FUM, n=5; diroximel fumarate, 3 and dimethyl fumarate, 2) received BNT162b2 (Pfizer, n=15) or mRNA-1273 (Moderna, n=7) vaccines. Blood samples were collected before and after each of the two vaccine doses, and 2 months after second vaccine dose. Anti-SARS-CoV-2 spike protein titers were measured using quantitative assay (Labcorp). Antibody neutralization was measured with a lentivirus-based pseudovirus particle expressing the D614 spike protein (Labcorp-Monogram Biosciences). T-cell reactivity was determined by measuring interferon-gamma and interleukin-2 in response to stimulation with SARS-CoV-2 peptides.

Results All patients in NTZ and FUM cohorts, but only 22% (2/9) of OCR cohort developed anti-spike and neutralizing antibodies. The highest titers were measured after the second vaccine dose, without significant difference between the NTZ and FUM cohorts in anti-spike IgG (69.7+/-55.1 vs 56.0+/-36.7 arbitrary units/ml) or neutralizing ID₅₀ (1513+/-1317 vs 942+/-566). Two months after the second vaccine, the antibody titers and neutralizing ID₅₀ decreased by 72% and 79% in NTZ cohort, respectively, and by 45% and 49% in FUM cohort. T-cell reactivity was observed in all cohorts as early as 7 days after the first vaccine, and further increased following the second vaccine.

Conclusions Patients on NTZ and FUM mounted robust antibody responses to SARS-CoV-2 mRNA vaccines, in contrast to OCR-treated patients. T-cell responses were comparable among all three treatment cohorts. Two months after the second vaccine, the serological responses decreased by 45-79%. These findings may inform the optimal timing of additional vaccine doses for MS patients.

Authors/Disclosures
Pavle Repovic, MD, PhD (Multiple Sclerosis Center) PRESENTER	Dr. Repovic has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Repovic has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Repovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Repovic has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Repovic has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Repovic has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for BristolMyersSquibb. Dr. Repovic has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Repovic has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for TG therapeutics. The institution of Dr. Repovic has received research support from Genentech. The institution of Dr. Repovic has received research support from Biogen.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Kelly Y. Chun, PhD (Labcorp)	Dr. Chun has nothing to disclose.
Christos J. Petropoulos, PhD (Monogram Biosciences, LabCorp)	Dr. Petropoulos has received personal compensation for serving as an employee of Labcorp-Monogram Biosciences. Dr. Petropoulos has stock in Laboratory Corporation of America Holdings. Dr. Petropoulos has received intellectual property interests from a discovery or technology relating to health care.
James D. Bowen, MD (Swedish Neuroscience Institute)	Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen IDEC. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for BristolMyers Squibb. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Bowen has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Bowen has received research support from Biogen IDEC. The institution of Dr. Bowen has received research support from Genentech. The institution of Dr. Bowen has received research support from Genzyme. The institution of Dr. Bowen has received research support from Novartis. The institution of Dr. Bowen has received research support from Roche.
Peiqing Qian, MD	Dr. Qian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Dr. Qian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Qian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Qian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS.
	No disclosure on file
	No disclosure on file
Jason Mendoza (Biogen)	No disclosure on file
Robin L. Avila, PhD (Biogen)	Mrs. Avila has received personal compensation for serving as an employee of Biogen. Mrs. Avila has stock in Biogen.
	No disclosure on file
	No disclosure on file

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