Immunity to hepatitis B has been successfully transferred by bone marrow transplantation, but has also occurred after liver transplantation (LTx). This study was designed to analyse the influence of alloreactivity and immunosuppression, on the efficacy of adoptive immune transfer to hepatitis B by liver transplantation. Orthotopic LTx (n = 34) were performed in three rat strain combinations representing different genetic constellations. Donors had been vaccinated twice with recombinant hepatitis B surface antigen while recipients were unimmunized. Half of the allogeneic recipients were immunosuppressed with cyclosporin A. All animals were monitored weekly for the presence of anti-hepatitis B surface antibodies (anti-HBs). Effective anti-HBs titres were detected in 85% (29/34) of liver recipients and lasted from 2 to 10 weeks. Donor titre above >15 000 mIU/mL ensured a 100% seroconversion rate in the recipients. The maximal anti-HBs titre in recipients represented 0.06% approximately 0.76% of the donor titre. Rejection reduced the adoptive immune transfer, which was protected by immunosuppression. These observations suggest that transfer of functionally active donor lymphocytes, deriving from the graft, contributed to the donor-derived immune response in the recipient. Further studies to augment the donor-derived immune response are warranted to ensure a therapeutic effect for the recipient at risk of reinfection.
Adoptive transfer of immunity to hepatitis B virus (HBV) is not provoked solely by bone marrow, but also by liver transplantation, although transiently. In the current study, simultaneous bone marrow transplantation, which possibly can increase the number of antibody-secreting cells, was performed to augment the efficacy of transferring HBV immunity. Stimulation of donor-derived immune cells by postoperative vaccination was used to investigate whether a secondary immune response can be induced in recipients. Orthotopic liver transplantation (n = 28), performed in three rat strain combinations representing different genetic constellations, was compared with bone marrow-augmented liver transplantation (n = 21). Donors had been vaccinated twice with recombinant hepatitis B surface antigen (HBsAg). Recipients surviving more than 10 weeks received a boost vaccination. All animals were monitored weekly for the presence of antibodies to HBsAg (anti-HBs). Effective anti-HBs titers were measured in 82% of liver recipients (23 of 28 recipients) and lasted from 2 to 9 weeks. Ninety percent of bone marrow-augmented liver recipients (19 of 21 recipients) seroconverted, with anti-HBs persisting from 2 to 12 weeks. A greater seroconversion rate, prolonged titer duration, and different pattern of titer development were observed in bone marrow-augmented liver recipients, although statistical significance could not be obtained because of the small numbers of comparable animals. Posttransplantation vaccination in recipients of combined grafts did not arouse a typical secondary antibody response, but showed a tendency toward an earlier and stronger response to vaccine in comparison to recipients without immune transfer. Simultaneous bone marrow transplantation showed an augmenting, but limited, effect on humoral immune transfer. Therefore, other potentially promising cellular strategies, such as transfer of in vivo and ex vivo stimulated antigen-specific cells should be pursued further. Improvement of the effect of postoperative vaccination possibly can be achieved by optimizing the immunization protocol.
Transfer of hepatitis B immunity occurs upon the transfer of immunologically active cells from the donor to the recipient by means of an organ graft. This has been repeatedly demonstrated for bone marrow and liver transplantations. Evidence is now presented for the transfer of anti-hepatitis B surface antibodies (anti-HBs) after kidney transplantation in rats. Kidney donors from one syngeneic and two allogeneic rat strains were immunized twice with 4 μg of recombinant hepatitis B vaccine. In week 6 after the first vaccination, kidney grafts were transplanted into Lewis (LEW) rats. Half of the recipients underwent daily immunosuppressive treatment with cyclosporin A (CsA). All recipients were vaccinated either after 10 weeks or 1 week postoperatively. Anti-HBs titer was measured weekly. Effective anti-HBs titers (10–227 mIU/ml, lasting for 1–7 weeks) were detected in 86% (25/29) of recipient rats, whose corresponding donors all had a titer above 15,000 mIU/ml. Immunosuppression enhanced the donor-derived immunity in terms of recipient-to-donor titer ratio, maximal titer and titer persistence.
Serogroup B meningococcal (MenB) vaccination recommendations for adolescents in the United States (US) include routine vaccination for all individuals at increased risk and vaccination for individuals not at increased risk aged 16–23 years (preferred age 16–18 years) based on shared clinical decision-making. The two licensed MenB vaccines require administration of ≥2 doses.This cross-sectional study analyzed 2017–2018 National Immunization Survey-Teen (NIS-Teen) data to evaluate ≥1 dose and ≥2 dose MenB vaccination coverage among adolescents aged 17 years. Multivariable logistic regression was used to further evaluate determinants of MenB vaccination.Nationally, MenB vaccination coverage among 17-year-olds increased from 14.5% in 2017 to 17.2% in 2018 for ≥1 dose and from 6.3% to 8.4% for ≥2 doses. MenB vaccination coverage (2017–2018) was the lowest in the South (≥1 dose: 14.6%; ≥2 doses: 6.3%) and highest in the Northeast region (18.3% and 9.3%), with variation observed by census division. Adolescents were more likely to have received ≥1 dose of MenB vaccine if they had any Medicaid insurance (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.32–2.39) or had received human papillomavirus (OR, 1.94; 95% CI, 1.41–2.67) or meningococcal A, C, W, and Y (OR, 4.03; 95% CI, 2.92–5.56) vaccinations.MenB first-dose coverage in the US is low, and even lower for a second dose, with regional variation. Being up to date with other routinely administered vaccines increased the likelihood of receiving MenB vaccination.
Introduction: As the number of organ donors remains stable, while the need for liver grafts is increasing, the use of partial liver grafts becomes more widely adopted. In the past, par-tial grafts were used only for children und small adults in order to transplant a liver mass adequate for the recipient. The lack of organs requires further extension of this practice using small-for-size grafts.
Bei dialysepflichtigen Patienten mit chronischem Nierenversagen kommt es häufig zur parenteralen Transmission von Hepatitis B Infektionen [1]. Die prophylaktische Impfung scheitert an der schlechten Ansprechrate auf das Impfantigen, ein generelles Problem chronisch Kranker. Bei niereninsuffizienten Patienten führt die Vakzination mit rekombinantem Impfstoff zu einer 50–80%igen Serokonversionsrate [2]. Patienten, die aufgrund ihrer Niereninsuffizienz transplantiert werden, haben ein noch hoheres Risiko einer Hepatitis B-Infektion [3] Ausserdem besteht die Gefahr der Reaktivierung einer durchgemachten Hepatitis B [4]. Die Therapie der Virusinfektion nach Transplantation gestaltet sich schwieriger als beim normalen Patienten, da die therapeutische Gabe von Interferon bei Transplantationsempfängern aufgrund des erhöhten Risikos der Induktion eines Abstoßungsreaktion nicht möglich ist [5].
Background: Patients with endstage renal disease as well as kidney transplant recipients have a high risk of a quiring hepatitis B infection and the response rate to active vaccination is very low in these patients. Previous experiments have shown that donor immunity can be transferred to a transplant recipient via the organ graft. This study aims to explore the efficacy of adoptive transfer of immunity by kidney transplantation.Methods: Male ACI-rats were used as donors, male Lewis rats as kidney recipients. The donors were vaccinated -6 and -2 weeks prior to organ donation with recombinant Hepatitis B vaccine (Engerix(R)). The left kidney of the donor was removed and the kidney graft was transplanted in orthotopic position.. Half of the animals were treated with daily subcutanoeus injections of Cyclosporin in a dose of 5 mg/kg/day. Anti-Hbs titer in donor and recipient was measured weekly using a micro-particle enzyme-immuno assay (MEIA) (Abbott).Results: All recipients developed an anti-HBs titer of 28-144 IU/l, which corresponds to about 0.03-0.09% of the titer of the donor. The maximal titer was found at 1 week after transplantation and decreased continuously thereafter.Conclusion: Donor immunity can be transferrred after kidney transplantation to the same extent as after liver transplantation, although the number of passenger leucocytes is lower and the organ much smaller. Immunosuppressive treatment is not lowering the adoptive transfer of immunity. Possible clinical consequence of this finding is the mandatory vaccination of living kidney donors to prevent Hepatitis B-infection in kidney transplant recipients.
Voraussetzung für die klinische Knochenmarkstransplantation ist die komplette Ablation des empfängereigenen Knochenmarkes durch Ganzkörperbestrahlung und nachfolgende Ersatz mit Spenderknochenmark. Die Rekonstitution des Immunsystems des Empfängers dauert in der Regel einige Wochen. Adoptiver Transfer von Immunität vom Spender zum Empfänger gegenüber einer Anzahl von Infektionserregern [1, 2] ist nach klinischer und experimenteller Knochenmarkstransplantation beschrieben worden. In einer systematischen Studie konnten Shouvan und Ilan [3] anti-HBs-Antikörper bei zuvor negativen Empfängern eines Knochenmarkstransplantates von positiven Spendern nachweisen. Kürzlich berichteten sie [4] über den Einzelfall eines Patienten, dessen persitierende Hepatitis B-Infektion nach Transplantation des Knochenmarkes eines Hepatitis B immunen Spenders nicht mehr nachweisbar war, d.h. möglicherweise wurde die Virus-clearance durch den adoptiven Transfer von Hepatitis B Immunität von Spender auf Empfänger erzielt.
Post Hepatitis-B Cirrosis is one of the major indications For liver transplantation in adults, and reinfection of the graft occurs in 70% of the cases. We developed a rat model of adoptive transfer of immunity to Hep. B after liver transplantation thus possibly allowing prevention or rejection.