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- Al-Dury, Samer, et al.
(författare)
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Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination
- 2022
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Ingår i: JHEP Reports. - : Elsevier BV. - 2589-5559. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-gamma (IFN-gamma) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-gamma was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1st vaccination vs. 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, p = 0.003) and 36% remained devoid of reactivity after the 2nd vaccination vs. 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, p = 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses (p < 0.05 vs. Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.05) vaccination. Conclusions: Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures. Clinical trial registration: EudraCT 2021-000349-42 Lay summary: T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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| 2. |
- Einarsdottir, Sigrun, et al.
(författare)
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Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
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Tidskriftsartikel (refereegranskat)abstract
- Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlapS1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.
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| 3. |
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| 4. |
- Einarsdottir, Sigrun
(författare)
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Vaccine responses after chemotherapy or stem cell transplantation in patients with hematological malignancies
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevention of infections in patients with hematological malignancies is important given the inherent immune deficiency associated with these diseases and the immunosuppressive effects of treatment. This thesis investigated the efficacy of vaccines against various pathogens among patients with hematological disease receiving chemotherapy or stem cell transplantation, including the longevity of vaccine responses. Paper I examines serum antibody levels against tetanus, diphtheria, and polio after standard chemotherapy in 104 patients treated for lymphoma or acute leukemia at median 18 months after completing treatment. Antibody levels were analyzed by enzyme-linked immunosorbent assay or neutralization tests and were compared with levels in age- and sex-matched healthy controls (n=47) and pretreatment levels (n=73). For tetanus, the number of seronegative patients increased during treatment (24 vs. 12 %) and antibody levels were reduced. A similar trend was observed for antibody levels against diphtheria. Immunity against poliovirus of serotypes 1 and 3 was preserved. Paper II describes a clinical vaccine trial that assessed the humoral response to four doses of vaccine against tick-borne encephalitis (TBE). A TBE vaccine (FSME-IMMUN®) was given starting nine months post-transplant to autologous (n=53) and allogeneic (n=51) stem cell transplant recipients. Serum samples were obtained prior to each vaccine dose (at nine, 10, 12, and 21 months) and three months after the last dose. Seventy-seven percent of patients after allogeneic stem cell transplantation (allo-HCT) and 80% after autologous stem cell transplantation (auto-HCT) achieved seropositivity following the last vaccine dose, compared with 100% among healthy controls. Graft-versus-host disease and ongoing immunosuppression were associated with poor vaccine responses. Paper III examines SARS-CoV-2 serum antibodies and T cell responses ex vivo before and after the third dose of an mRNA vaccine among 40 allo-HCT recipients. Many patients responded well, with antibodies above the upper detection limit. However, 16% were seronegative following vaccination and 49% of patients showed no T-cell reactivity against SARS-CoV-2 peptides. Paper IV analyzes serum antibody levels against tetanus and diphtheria among 143 long-term survivors after allo-HCT who had been vaccinated according to standard protocol with three doses of diphtheria and tetanus vaccine. Diphtheria immunity was poor and 40% of patients were seronegative. However, all patients had detectable antibodies against tetanus. To conclude, diphtheria immunity is poor in adult patients receiving chemotherapy as well as in long-term survivors after allo-HCT, and boosters may be considered. Vaccination against TBE is immunogenic when starting nine months after allo- or auto-HCT. The third dose of mRNA vaccine against COVID-19 elicits antibody responses in a majority of allo-transplanted patients. However, T cell responses remain poor in a significant proportion of these patients.
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