Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases

Raptis, Catherine; Berger, Christoph; Ciurea, Adrian; Andrey, Diego O.; Polysopoulos, Christos; Lescuyer, Pierre; Maletic, Tanja; Riek, Myriam; Scherer, Almut; Loga, Isabell von; Safford, Judith; Lauper, Kim; Möller, Burkhard; Vuilleumier, Nicolas; Finckh, Axel; Rubbert-Roth, Andrea

doi:10.3389/fimmu.2022.1016927

Cited by 9 publications

(5 citation statements)

References 41 publications

(45 reference statements)

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“…Moreover, factors related with vaccine (such as vaccine type, product, adjuvant, and dose) and administration (schedule, site, route, time of vaccination, and coadministered vaccines and other drugs) are also important [ 13 , 27 ]. An understanding of all these factors and their impacts on the design of vaccine studies and decisions on vaccination schedules can help to improve vaccine immunogenicity and efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…An understanding of all these factors and their impacts on the design of vaccine studies and decisions on vaccination schedules can help to improve vaccine immunogenicity and efficacy. In fact, in a study carried out in the Swiss cohort (SCQM) including 565 patients, two-dose vaccination with mRNA1273 (Moderna) versus BNT162b2 (Pfizer) resulted in a higher anti-SARS-CoV-2 Ab levels [ 27 ]. In our study most patients (50) received the vaccination scheme with BNT162b2 (Pfizer) and only 8 patients were vaccinated with mRNA1273 (Moderna) as the first 2 doses.…”

Section: Discussionmentioning

confidence: 99%

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Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment

Plasencia-Rodríguez,

Martínez-Feito,

Hernández

et al. 2023

Allergy Asthma Clin Immunol

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Background Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients. Material and methods This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4–6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack. Results A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17–163) in patients vs 625 (405–932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%). Conclusion SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment

Plasencia-Rodríguez,

Martínez-Feito,

Hernández

et al. 2023

Allergy Asthma Clin Immunol

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“…Blue lines indicate two rituximab-treated patients, one diagnosed with SLE and the other with Sjogren's. Rituximab-treated patients were separated because rituximab is known to have significantly negative effects on the humoral immune response to SARS-CoV-2 mRNA vaccines (2,(9)(10)(11).…”

Section: Robust Humoral Immune Response To Covid-19 Mrna Vaccine In R...mentioning

confidence: 99%

Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients

Zhou

et al. 2023

Preprint

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Objective. To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases. Methods. We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogrens syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry. Results. Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable. Conclusion. Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.

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“…Immunomodulatory drugs used by IA patients are seen as the main reason for the reduced post-vaccination immune response. Immunomodulatory drugs that reduce the immunogenicity of COVID-19 vaccines to the greatest extent are rituximab [ 4 , 6 , 8 , 9 , 10 , 13 , 14 , 17 , 19 , 20 , 21 , 22 ], glucocorticosteroids (GCs) [ 4 , 10 , 12 , 14 , 15 , 16 , 19 , 21 ], and abatacept [ 13 , 14 , 16 , 22 , 23 ], with single studies, also showing a decrease in the humoral response after methotrexate (MTX) [ 8 , 11 , 12 , 14 , 15 ], TNF inhibitors [ 7 , 15 , 22 , 24 ], IL-6 inhibitors [ 23 ], and JAK inhibitors [ 8 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients

Wroński

Jaszczyk

Roszkowski

et al. 2023

Viruses

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Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

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Type of mRNA COVID-19 vaccine and immunomodulatory treatment influence humoral immunogenicity in patients with inflammatory rheumatic diseases

Cited by 9 publications

References 41 publications

Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment

Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment

Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients

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