| 1. |
|
|
| 2. |
- Al-Dury, S., et al.
(författare)
-
Catch-up antibody responses and hybrid immunity in mRNA vaccinated patients at risk of severe COVID-19
- 2023
-
Ingår i: Infectious Diseases. - 2374-4235. ; 55:10, s. 744-750
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe immunogenicity of repeated vaccination and hybrid immunity in vulnerable patients remains unclear.MethodsWe studied the impact of iterative Covid-19 mRNA vaccination and hybrid immunity on antibody levels in immunosuppressed subjects. Patients with liver cirrhosis (n = 38), survivors of allogeneic haematopoietic stem cell transplantation (allo-HSCT) (n = 36) and patients with autoimmune liver disease (n = 14) along with healthy controls (n = 20) were monitored for SARS-CoV-2-S1 IgG after their 1st-3rd vaccine doses, 31 of whom became infected with the Omicron variant after the 2nd dose. Ten uninfected allo-HSCT recipients received an additional 4th vaccine dose.ResultsUnexpectedly, immunosuppressed patients achieved antibody levels in parity with controls after the 3rd vaccine dose. In all study cohorts, hybrid immunity (effect of vaccination and natural infection) resulted in approximately 10-fold higher antibody levels than vaccine-induced immunity alone.ConclusionsThree doses of the Covid-19 mRNA vaccine entailed high antibody concentrations even in immunocompromised individuals, and hybrid-immunity resulted further augmented levels than vaccination alone.
|
|
| 3. |
- Al-Dury, Samer, et al.
(författare)
-
Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination
- 2022
-
Ingår i: JHEP Reports. - : Elsevier BV. - 2589-5559. ; 4:7
-
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).
|
|
| 4. |
- Einarsdottir, Sigrun, et al.
(författare)
-
Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity.
- 2022
-
Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 6:9, s. 2723-2730
-
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.
|
|
| 5. |
- Einarsdottir, Sigrun, et al.
(författare)
-
Humoral immunity to tetanus, diphtheria and polio in adults after treatment for hematological malignancies
- 2020
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 38:5, s. 1084-1088
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction After chemotherapy, children with acute lymphocytic leukemia lose immunity and need revaccination against tetanus and diphtheria. However, little is known about immunity in adult patients after treatment for hematological malignancies. In this study, we assessed serology levels against polio, diphtheria and tetanus in adult patients after conventional treatment for leukemia and lymphoma. Patients One hundred and four patients, age 61 (19–86) years, were included at a median of 18 (4–77) months after chemotherapy for acute leukemia (n = 24) or lymphoma (n = 80). Pre-treatment sera were available in 73 cases for a pre-versus post treatment comparison. Healthy, age- and sex matched controls were available for 47 pts. Methods Tetanus antibodies were quantified using ELISA, and antibody levels ≥0.01 IU/mL were considered protective. Diphtheria antibodies were analyzed using neutralization test (n = 60) or by ELISA (n = 44). In both tests values ≥0.01 IU/mL were considered protective. Antibodies against poliovirus serotype 1 and 3 were assessed by a neutralizing test. A microneutralization titer of ≥2 was considered protective. Results Tetanus: There were significantly more non-immune patients after treatment (24%), compared to before (12%), p = 0.02. Post-treatment antibody levels were significantly lower than pre-treatment levels (p = 0.02). Diphtheria: There was a trend, p = 0.06, towards more non-immune patients after treatment (21%) compared to before (27%). Antibody levels post treatment were lower than pre treatment levels (p = 0.03) and lower than controls (p = 0.01). Polio: There was no significant difference in the number of non-immune patients before vs after chemotherapy for either PV1 or PV3. Protective immunity against serotype 1 and 3 was preserved in 90 and 97%, respectively. Conclusions After standard chemotherapy for leukemia and lymphoma a significant proportion of patients had impaired humoral immunity to diphtheria and tetanus. However, polio immunity was well preserved.
|
|
| 6. |
|
|
| 7. |
- Einarsdottir, Sigrun, et al.
(författare)
-
Long-Term Immunity Against Tetanus and Diphtheria after Vaccination of Allogeneic Stem Cell Transplantation Recipients
- 2023
-
Ingår i: Transplantation and Cellular Therapy. - : Elsevier BV. - 2666-6375 .- 2666-6367. ; 29:4
-
Tidskriftsartikel (refereegranskat)abstract
- Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplantation (HCT) is usually effective, but the duration of the immunity is unknown. We conducted this study to evaluate humoral immunity to tetanus and diphtheria in long-term survivors and to provide knowledge regarding the need for boosters. The median time from HCT to blood sampling was 14 years (range, 8 to 40 years). All patients had received at least 3 doses of vaccines against both tetanus and diphtheria, either monovalent or combination vaccines containing a full dose of the diphtheria toxoid component. In addition, 1 or more booster doses were administered to 21 of the 146 patients (14%). On enzyme-linked immunosorbent assay, levels <.1 IU/mL for diphtheria and <.01 IU/mL for tetanus were considered low or seronegative. Values between .01 and .5 IU/mL for tetanus and between .1 and 1.0 IU/mL for diphtheria were considered to represent partial protection, and levels >.5 and >1.0 IU/mL were considered high and protective, respectively. In all, 39% of patients were seronegative against diphtheria, 52% had some protection, and 9% had a high titer. In contrast, no patient had become seronegative to tetanus, 32% had "partial protection" against tetanus and 68% had a high titer. In multivariate analysis, active graft-versus-host-disease, sex, or time from sampling did not affect the probability of becoming seronegative or seropositive. Younger age was associated with lower antibody levels to tetanus toxoid, but age was not correlated with antibody levels against diphtheria toxoid. Tetanus immunity was maintained after vaccination in most longterm survivors, but immunity against diphtheria was poor, and boosters should be considered. (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
|
|
| 8. |
|
|
| 9. |
- Einarsdottir, Sigrun, et al.
(författare)
-
Vaccination against tick-borne encephalitis (TBE) after autologous and allogeneic stem cell transplantation
- 2021
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 39:7, s. 1035-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Our aim was to assess response and side effects of 4 doses of TBE vaccine to patients (pts) after allo- and autologous stem cell transplantation (SCT). PATIENTS: Included were 104 pts with leukaemia, myeloma and lymphoma, median age 61 yrs. METHODS: Vaccine (FSME-Immun (R)) was given at 9, 10, 12, and 21 months post-transplant. Serum samples were obtained before and after vaccinations. Healthy controls (n = 27) received 3 vaccinations. Assessments of TBE specific IgG antibodies were performed by Enzygnost anti-TBE ELISA test (Siemens, Sweden). Results: Antibody levels (>12 U/mL; "seropositivity") were seen in 77% and 80% of pts after allo- and autoSCT; IgG levels; 89 vs 94 U/mL. Ongoing chronic GvHD and immunosuppression (n = 29) was associated with sero-negativity in the last sample (p = 0.007). All controls (n = 27) developed protective antibody levels. Conclusions: TBE vaccination was safe, and 4 doses starting 9 months post-SCT, induced seropositivity in a vast majority of pts. (C) 2021 Elsevier Ltd. All rights reserved.
|
|
| 10. |
- Einarsdottir, Sigrun
(författare)
-
Vaccine responses after chemotherapy or stem cell transplantation in patients with hematological malignancies
- 2022
-
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.
|
|
