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Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

ABSTRACT: Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and COVID-19 vaccination. Here, the humoral and cellular responses are analyzed in a group of aCD20-MS patients (n=43) compared to a healthy control cohort (n=34) during the first 6 months after a 2-dose cycle mRNA-based COVID-19 vaccination. Both IgG antibodies recognizing receptor binding domain (RBD) from CoV-2 spike protein and their blocking activity against RBD-hACE2 binding were significantly reduced in aCD20-MS patients, with a seroconversion rate of only 23.8%. Interestingly, even under conditions of severe B-cell depletion and failed seroconversion, a significantly higher polyfunctional IFNγ⁺ and IL-2⁺ T-cell response and strong T-cell proliferation capacity were detected compared to controls. Moreover, no difference in T-cell response was observed between forms of disease (relapsing remitting- vs progressive-MS), anti-CD20 therapy (Rituximab vs Ocrelizumab) and type of mRNA-based vaccine received (mRNA-1273 vs BNT162b2). These results suggest the generation of a partial adaptive immune response to COVID-19 vaccination in B-cell depleted MS individuals driven by a functionally competent T-cell arm. Investigation into the role of the cellular immune response is important to identifying the level of protection against SARS-CoV-2 in aCD20-MS patients and could have potential implications for future vaccine design and application.

SUBMITTER: Alfonso-Dunn R

PROVIDER: S-EPMC9388928 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

Alfonso-Dunn Roberto R Lin Jerry J Kirschner Vanessa V Lei Joyce J Feuer Grant G Malin Michaela M Liu Jiayuan J Roche Morgan M Sadiq Saud A SA

Frontiers in immunology 20220805

Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and ...[more]

PMID: 35990701

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Project description:Multiple sclerosis patients treated with anti-CD20 therapy (aCD20-MS) are considered especially vulnerable to complications from SARS-CoV-2 infection due to severe B-cell depletion with limited viral antigen-specific immunoglobulin production. Therefore, multiple vaccine doses as part of the primary vaccination series and booster updates have been recommended for this group of immunocompromised individuals. Even though much less studied than antibody-mediated humoral responses, T-cell responses play an important role against CoV-2 infection and are induced efficiently in vaccinated aCD20-MS patients. For individuals with such decoupled adaptive immunity, an understanding of the contribution of T-cell mediated immunity is essential to better assess protection against CoV-2 infection. Here, we present results from a prospective, single-center study for the assessment of humoral and cellular immune responses induced in aCD20-MS patients (203 donors/350 samples) compared to a healthy control group (43/146) after initial exposure to CoV-2 spike antigen and subsequent re-challenges. Low rates of seroconversion and RBD-hACE2 blocking activity were observed in aCD20-MS patients, even after multiple exposures (responders after 1st exposure = 17.5%; 2nd exposure = 29.3%). Regarding cellular immunity, an increase in the number of spike-specific monofunctional IFNγ+-, IL-2+-, and polyfunctional IFNγ+/IL-2+-secreting T-cells after 2nd exposure was found most noticeably in healthy controls. Nevertheless, a persistently higher T-cell response was detected in aCD20-MS patients compared to control individuals before and after re-exposure (mean fold increase in spike-specific IFNγ+-, IL-2+-, and IFNγ+/IL-2+-T cells before re-exposure = 3.9X, 3.6X, 3.5X/P< 0.001; after = 3.2X, 1.4X, 2.2X/P = 0.002, P = 0.05, P = 0.004). Moreover, cellular responses against sublineage BA.2 of the currently circulating omicron variant were maintained, to a similar degree, in both groups (15-30% T-cell response drop compared to ancestral). Overall, these results highlight the potential for a severely impaired humoral response in aCD20-MS patients even after multiple exposures, while still generating a strong T-cell response. Evaluating both humoral and cellular responses in vaccinated or infected MS patients on B-cell depletion therapy is essential to better assess individual correlations of immune protection and has implications for the design of future vaccines and healthcare strategies.

Project description:BackgroundVaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).MethodsPwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty®) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.ResultsThirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.ConclusionsThe evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.

Dataset Information

Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

Publications

Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

Similar Datasets

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