Efficacy and safety of SARS-CoV-2 revaccination in non-responders with immune-mediated inflammatory disease

Simón, David; Taşçılar, Koray; Fagni, Filippo; Schmidt, Katja; Krönke, Gerhard; Kleyer, Arnd; Ramming, Andreas; Schoenau, Verena; Bohr, Daniela; Knitza, Johannes; Harrer, Thomas; Manger, Karin; Manger, Bernhard; Schett, Georg

doi:10.1136/annrheumdis-2021-221554

Cited by 46 publications

(68 citation statements)

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“…In a cohort of 33 patients treated with rituximab who did not respond to two injection, only 21% harbour neutralising antibodies after a booster vaccination. 28 The discrepancy in response is most likely due to variation in the extent of B-cell depletion as suggested by other studies. 20 29 30 Our results are in line with these observations, and suggest that a third dose is needed, mainly in patients with low responses after two doses, but not sufficient, in most RTX-treated individuals.…”

Section: Discussionmentioning

confidence: 82%

“…A third dose of vaccine had no effect on B-cell response in patients treated with rituximab but it significantly increased anti-spike IgG levels and neutralisation activity against both variants in patients with methotrexate and cDMARDs compared with those receiving only two doses. In a cohort of 33 patients treated with rituximab who did not respond to two injection, only 21% harbour neutralising antibodies after a booster vaccination 28. The discrepancy in response is most likely due to variation in the extent of B-cell depletion as suggested by other studies 20 29 30.…”

Section: Discussionmentioning

confidence: 86%

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Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

et al. 2022

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ObjectivesThe emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases.MethodsProspective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety.ResultsSixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses.ConclusionRituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (ClinicalTrials.gov number, NCT04870411).

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 86%

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

et al. 2022

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“…Our main finding is, thus, that after a third dose of SARS-CoV-2 mRNA vaccines, only a subset of patients mounts a humoral immune or CMI response. Emerging reports by others have found a similar rate of around 25% de novo antispike seroconversion after a third dose of SARS-CoV-2 vaccines in patients on anti-CD20 therapies that were humoral non-responders after a two-dose vaccination scheme 8–10 18–23. Several studies that used EliSpot or activation-induced markers to semiquantitatively assess CMI revealed higher rates of CMI than humoral responses after a third SARS-CoV-2 vaccine in patients with autoimmune diseases under anti-CD20 treatment 8 19 24–26.…”

Section: Discussionmentioning

confidence: 83%

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

et al. 2022

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BackgroundThe majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients.MethodsWe investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6–4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression.Results5.6 months (IQR: 5.1–6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0–7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants.ConclusionThis study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

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“…Increasing vaccine immunogenicity by the use of heterologous prime‐boost vaccination scheme seems an attractive option. However, when applied for the third vaccine dose in patients with immune‐mediated inflammatory diseases or treated with Rituximab, this strategy did not increase response rates compared to an homologous 3D mRNA vaccine 36,37 . An alternative option is the passive immunization with anti‐SARS‐CoV‐2 monoclonal antibodies, a primary prevention strategy which was recently successfully tested in people with household exposure to SARS‐CoV‐2 38 …”

Section: Discussionmentioning

confidence: 99%

Predictive factors of a viral neutralizing humoral response after a third dose of COVID-19 mRNA vaccine

Charmetant

Espi

Barba

et al. 2022

American Journal of Transplantation

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Kidney transplant recipients (KTRs) have reduced ability to mount adequate antibody response after two doses of the COVID‐19 mRNA vaccine. French health authorities have allowed a third booster dose (D3) for KTRs, but their response is heterogeneous and tools able to discriminate the responders are lacking. Anti‐RBD IgG titers (chemiluminescence immunoassay), spike‐specific cellular responses (IFN‐γ‐releasing assay, IGRA), and in vitro serum neutralization of the virus (the best available correlate of protection), were evaluated 7–14 days after the second dose (D2) of BNT162b2 vaccine in 93 KTRs. Among the 73 KTRs, whose serum did not neutralize SARS‐CoV‐2 in vitro after D2, 14 (19%) acquired this capacity after D3, and were considered as “responders.” Exploratory univariate analysis identified short time from transplantation and high maintenance immunosuppression as detrimental factors for the response to D3. In addition, any of the presence of anti‐RBD IgGs and/or positive IGRA after D2 was predictive of response to D3. By contrast, none of the KTRs with both a negative serology and IGRA responded to D3. In summary, routinely available bioassays performed after D2 allow identifying KTRs that will respond to a booster D3. These results pave the way for the personalization of vaccination strategy in KTRs.

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Efficacy and safety of SARS-CoV-2 revaccination in non-responders with immune-mediated inflammatory disease

Cited by 46 publications

References 17 publications

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

Predictive factors of a viral neutralizing humoral response after a third dose of COVID-19 mRNA vaccine

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