Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Abstract

BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients

“…In our setting, an uneven T-cell subset distribution was observed, in which IFNγ-IL2-TNFα+ and IFNγ-IL2+TNFα--producing T-cells prevailed. Since the quality of T-cell response, characterized by a multifunctional profile, has been associated with higher protection in response to infections and vaccinations [ 6 , 7 , 8 , 36 , 37 ], the highly uneven subset distribution of T-cells found in our cohort might indicate a qualitatively inferior T-cell response to vaccination. However, after twelve months since the third dose of the SARS-CoV-2 mRNA-based vaccine, a dynamic change in the subset distribution was observed, in which a more heterogeneous distribution, like HD ones, was observed in SOT-Rs as well.…”

“…T-cell-specific response was assessed using a multiparametric flow cytometry after overnight stimulation, as previously described [ 8 , 27 ]. Moreover, to assess the Omicron variant T-cell response, PepTivator SARS-CoV-2 Prot_S B.1.1.529/BA.5 Mutation Pool (Milteny Biotec, Bergisch Gladbach, Germany) that covers selectively mutated regions was used to supplement PepTivators covering the sequence of the wild type of spike glycoprotein (“S”) in order to detect immune responses towards all three variants: Wuhan (wild type), B.1.1.529/BA.4, and B.1.1.529/BA.5 variant.…”

“…In this context, mRNA-based vaccines have become the mainstay for the pandemic response, due to their ability to induce robust and protective humoral and cellular responses against SARS-CoV-2 [ 4 , 5 ]. However, in immunocompromised subjects, low rates of anti-Spike (anti-S) antibody levels and moderate vaccine effectiveness have been observed [ 3 , 6 , 7 , 8 ].…”

Evaluation of BAFF, APRIL and CD40L in Ocrelizumab-Treated pwMS and Infectious Risk

“…Finally, B cells are involved in the response to infections [ 48 , 49 ] and vaccination [ 50 , 51 ]. Thus, in the present study, the B cell activation markers BAFF, APRIL and CD40L were analyzed longitudinally in pwMS treated with ocrelizumab, correlating these findings to the occurrence of infectious events.…”

A prospective longitudinal cohort study on risk factors for COVID-19 vaccination failure (RisCoin): methods, procedures and characterization of the cohort

“…Nevertheless, for other diseases, such as influenza, immunosuppression is known to attenuate the vaccine response [ 19 ]. Along these lines, first publications in patients under immunosuppressive therapy have already shown that, depending on the disease and the medication, the immune response to SARS-CoV-2 infection detected by PCR and COVID-19 vaccination may be severely attenuated or even absent [ 20 – 22 ].…”