Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Aiello, Alessandra; Coppola, Andrea; Ruggieri, Serena; Farroni, Chiara; Altera, Anna Maria Gerarda; Salmi, Andrea; Vanini, Valentina; Cuzzi, Gilda; Petrone, Linda; Meschi, Silvia; Lapa, Daniele; Bettini, Aurora; Haggiag, Shalom; Prosperini, Luca; Galgani, Simonetta; Quartuccio, Maria Esmeralda; Bevilacqua, Nazario; Garbuglia, Anna Rosa; Agrati, Chiara; Puro, Vincenzo; Tortorella, Carla; Gasperini, Claudio; Nicastri, Emanuele; Goletti, Delia

doi:10.1136/jnnp-2022-330175

Cited by 17 publications

(19 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, the T-cell response rate remained stable throughout the study. These findings resemble the kinetics pattern previously reported by Farroni et al 41 and Aiello et al 37 in other immunosuppressed populations, including patients with multiple sclerosis and rheumatoid arthritis undergoing treatment with various disease-modifying therapies. Interestingly, in those studies, 37,41 the T-cell specific SARS-CoV-2 response was mainly driven by CD4 + T-cells, which could justify the impact of a pre-vaccination low CD4 + cell count in the impairment of cellular response found in our study.…”

Section: As Previously Described By Alimam Et Al and Mariotti Et Alsupporting

confidence: 89%

“…Consistently with the findings in these studies, 8,36 the main factors related to a poor humoral response after a third vaccine dose were hypogammaglobulinemia, lymphopenia, low CD19 + cell count, and above all, active treatment with anti‐CD20 monoclonal antibodies. The deleterious effect of anti‐CD20 therapy in humoral immunogenicity has also been described by Aiello et al 37 and Tortorella et al 38 in patients with multiple sclerosis treated with ocrelizumab, which also failed to achieve seroconversion after booster SARS‐CoV‐2 vaccination.…”

Section: Discussionmentioning

confidence: 59%

See 1 more Smart Citation

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS‐CoV‐2 booster vaccination in hematologic neoplasms

Jiménez

Fernández‐Naval

Navarro³

et al. 2023

American J Hematol

View full text Add to dashboard Cite

Data on the effect of booster SARS‐CoV‐2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine‐induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA‐1273 SARS‐CoV‐2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS‐CoV‐2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti‐S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti‐CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+, CD4+, CD56+ cell count determined an impaired cellular response. After 13.8 months of follow‐up, the incidence of SARS‐CoV‐2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN‐γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti‐S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS‐CoV‐2 booster vaccination improves humoral response and COVID‐19 severity is associated with impaired vaccine‐induced immunogenicity.

show abstract

Section: As Previously Described By Alimam Et Al and Mariotti Et Alsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 59%

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS‐CoV‐2 booster vaccination in hematologic neoplasms

Jiménez

Fernández‐Naval

Navarro³

et al. 2023

American J Hematol

View full text Add to dashboard Cite

show abstract

“…Altogether, the T‐cell response was reduced in some individuals below the cutoff level for all other DMT groups ranging from minor impact in alemtuzumab and teriflunomide to more variable responses in natalizumab‐, cladribine‐ and dimethylfumarate‐treated pwMS. Reduced T‐cell responses to peptides have been described previously for cladribine and natalizumab [21, 24], and a third vaccination led to higher proportions of Th1 and IFN‐γ‐specific CD4+ T‐cell responders in pwMS [43].…”

Section: Discussionmentioning

confidence: 86%

“…A third dose of the SARS‐CoV‐2 vaccine has been previously shown to boost antibody levels in fingolimod‐treated individuals; however, other studies show that a considerable number of pwMS still do not develop antibodies after a third vaccination [25, 41–43].…”

Section: Discussionmentioning

confidence: 99%

The impact of hybrid immunity on immune responses after SARS‐CoV‐2 vaccination in persons with multiple sclerosis treated with disease‐modifying therapies

Rabenstein,

Thomas,

Carlin

et al. 2023

Euro J of Neurology

View full text Add to dashboard Cite

IntroductionHybrid immunity to SARS‐CoV‐2 develops from a combination of natural infection and vaccine‐generated immunity. Multiple sclerosis (MS) disease modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS‐CoV‐2 vaccination and infection.ObjectivesTo compare antibody and T‐cell responses after SARS‐CoV‐2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs. To assess differences between naïvely‐vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS‐CoV‐2 infection.MethodsWe determined antibody and T‐cell responses in pwMS at baseline, 4 and 12 weeks after the second dose of SARS‐CoV‐2 vaccination in 143 pwMS with or without previous SARS‐CoV‐2 infection and in 40 healthy controls (HC). The MS cohort compromised: natalizumab (n=22), dimethylfumarate (n=23), fingolimod (n=38), cladribine (n=30), alemtuzumab (n=17) and teriflunomide (n=13) treated pwMS. IgG antibody responses to SARS‐CoV‐2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T‐cell responses (IFNγ and IL13).ResultsHumoral and T‐cell responses to vaccination were comparable between naïvely‐vaccinated HC and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod‐treated pwMS. Both fingolimod‐treated pwMS and HC vaccinated following a previous SARS‐CoV‐2 infection had higher antibody levels four weeks after vaccination compared to naïvely‐vaccinated individuals. Antibody and IFNγ‐levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine.ConclusionThese findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.

show abstract

“…43 Robust longitudinal cellular immunity in B-cell-depleted MS patients is a consistent finding across multiple studies. 26,33,[44][45][46][47] Booster further raised cytokine responses 4-5-fold. This was a similar-fold increase as after the primary vaccine.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

Kister,

Curtin,

Piquet

et al. 2024

Preprint

View full text Add to dashboard Cite

Objectives: 1. To plot the trajectory of humoral and cellular immune responses to the primary (two-dose) COVID-19 mRNA series and the third/booster dose in B-cell-depleted multiple sclerosis (MS) patients up to 2 years post-vaccination; 2. to identify predictors of immune responses to vaccination; and 3. to assess the impact of intercurrent COVID-19 infections on SARS CoV-2-specific immunity. Methods: 60 Ocrelizumab-treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre-vaccination, and then 4, 12, 24, and 48 weeks post-primary series, and 4, 12, 24, and 48 weeks post-booster. Binding anti-Spike antibody responses were assessed with multiplex bead-based immunoassay (MBI) and electrochemiluminescence (Elecsys©, Roche Diagnostics), and neutralizing antibody responses with live-virus immunofluorescence-based microneutralization assay. Spike-specific cellular responses were assessed with IFNγ/IL-2 ELISpot (Invitrogen) and, in a subset, by sequencing complementary determining regions (CDR)-3 within T-cell receptors (Adaptive Biotechnologies). A linear mixed effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results: The primary vaccination induced an 11-208-fold increase in binding and neutralizing antibody levels and a 3-4-fold increase in IFNγ/IL-2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3-5-fold increase in binding antibodies and 4-5-fold increase in IFNγ/IL-2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation: Humoral and cellular benefits of COVID-19 vaccination in B-cell-depleted MS patients were sustained for up to 2 years when booster doses were administered.

show abstract

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Cited by 17 publications

References 46 publications

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS‐CoV‐2 booster vaccination in hematologic neoplasms

Kinetics of cellular and humoral immunogenicity and effectiveness of SARS‐CoV‐2 booster vaccination in hematologic neoplasms

The impact of hybrid immunity on immune responses after SARS‐CoV‐2 vaccination in persons with multiple sclerosis treated with disease‐modifying therapies

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

Contact Info

Product

Resources

About