Preserved T cell but attenuated antibody response in MS patients on Fingolimod and Ocrelizumab following 2ndand 3rdSARS-CoV-2mRNA vaccine

ABSTRACT

Introduction: Immunosuppressed patients may not mount an adequate immune response to 2 doses of SARS-CoV-2 mRNA vaccine and are eligible to receive a 3rddose. There is limited knowledge about T cell responses specifically in patients with multiple sclerosis (MS) who receive 3 doses of vaccine. Objectives & Aims: To assess the SARS-CoV-2 spike antibody responses and T cell responses in MS patients on high efficacy immunotherapies and healthy controls (HC) who received 2 and 3 doses of SARS-CoV-2 mRNA vaccines. Method(s) This is a study of patients with MS, aged 18-65, on fingolimod (FIN) and ocrelizumab (OCR) for at least 3 months prior to 1stmRNA SARS-CoV-2 vaccine dose (BNT162b2 or mRNA- 1273) and a cohort of HC. Blood samples were collected after 2nd(2- vax) and 3rd(3-vax) dose of mRNA vaccine. The proportion of patients and HC who exhibited seroconversion, demonstrating serum SARS-CoV-2 spike antibody levels >0.4 U/ml,was determined. T cell responses were examined in a subgroup of patients with MS and HC after 2-vax and 3-vax by flow cytometry. Result(s) The proportion of patients who seroconverted after 2-vax was 8/33 (24.2%) in the OCR group, 5/7 (71.4%) in the FIN group, and 29/29 (100%) in the HC group (Fisher's exact test,P=5.7*10-11). After 3-vax, 9/21 (40.9%) patients in the OCR group seroconverted as compared to 19/21 (90.5%) in the FIN group, and 7/7 (100%) in the HC group (Fisher's exact test for difference,P=0.0003). There was SARS-CoV-2 peptide reactive CD4+ and CD8+ T cell activation across all 3 groups (OCR 2-vax n=10, FIN 2-vax n=6, HC 2-vax n=8, OCR 3-vax n=9, FIN 3-vax n=10, HC 3-vax n=5) as compared to unstimulated condition after 2-vax and 3-vax (Mixed effects analysis,P<0.0001). There was an increase in the percentage of SARS-CoV-2 peptide reactive CD4+ T cells in HC and OCR group but not in FINgroupafter 2-vax and 3-vax. There was anincrease in the percentage ofIFNgammaandTNFalphaproducing CD4+ and CD8+ T cells in FIN group as compared to HC and OCR group after 2-vax and 3-vax.TNFalphaproducing central memory CD4+ T cells were increased in OCR group after 2-vax andIFNgammaandTNFalphaproducing effector memory and terminally differentiated effector memory CD4+ T cells were increased in FIN group after 2-vax and 3-vax as compared to HC. Conclusion(s) MS patients on ocrelizumab and fingolimod had decreased spike antibody responses, but preserved T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination.