Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation

Lindemann, Monika; Barsegian, Vahé; Runde, Volker; Fiedler, Melanie; Heermann, Klaus-Hinrich; Schaefer, U. W.; Roggendorf, Michael; Grosse‐Wilde, H.

doi:10.1097/01.tp.0000054841.42796.68

Cited by 38 publications

(26 citation statements)

References 24 publications

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“…Adoptive transfer of immunity to HBV was first studied in allogeneic stem cell and bone marrow transplantation [115][116][117][118][119]. Studies in several animal models and human trials have already demonstrated that immunity to HBV can be adoptively transferred, even in the setting of organ transplantation [120][121][122][123].…”

Section: Adoptive Transfer Of Immunity To Hbv In Liver Transplant Recmentioning

confidence: 98%

Hepatitis B and liver transplantation: 2008 update

Beckebaum

Sotiropoulos

Gerken

et al. 2008

Reviews in Medical Virology

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The ultimate goal of treatment is suppression of viral replication to undetectable HBV-DNA levels prior to and after liver transplantation (LT) to prevent infection of the newly transplanted liver. Most published data are available from therapy with lamivudine (LAM) in pre- and post-transplant HBV patients. Add-on therapy with adefovir dipivoxil (ADV) in pre-transplant LAM-resistant patients has been shown to represent an effective antiviral strategy leading to hepatic recompensation in many cases and, eventually, removal from the waiting list. Newer nucleos(t)ide analogues such as entecavir, tenofovir and telbivudine have shown lower resistance rates than LAM and more antiviral potency in studies in the non-transplant setting. Combined hepatitis B immune globulin (HBIG) and nucleos(t)ide analogue therapy have been widely adopted as the most effective treatment strategy against recurrent HBV disease after LT. Many programs have evaluated lower doses or a shorter duration of HBIG and intramuscular versus intravenous routes of administration. Active immunisation using recombinant HBV vaccines, including the S, pre-S1 and pre-S2 regions, and those with immunostimulatory adjuvants, seem to be more immunogenic than the currently available vaccines and have been used in studies to replace HBIG. Furthermore, it has been shown that immune memory against HBV can be adoptively transferred from organ donors to transplant recipients. Nucleos(t)ide analogue combination therapies might provide an alternative to the current treatment paradigm with costly HBIG; however, experience with this new treatment regimen is very limited and controlled clinical studies are urgently warranted to investigate its safety and efficacy and to determine which nucleos(t)ide analogue combinations will be the most promising in the long term after LT.

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Section: Adoptive Transfer Of Immunity To Hbv In Liver Transplant Recmentioning

confidence: 98%

Hepatitis B and liver transplantation: 2008 update

Beckebaum

Sotiropoulos

Gerken

et al. 2008

Reviews in Medical Virology

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“…These cells replicate actively and are responsible for the acquisition of donor immunity in allogeneic recipients. [60][61][62] Vector insertions in these cells and in other committed lineages, which can be transformed, 63,64 may increase the risk of insertional activation of proto-oncogenes such as LMO-2. We did not observe leukemias in any of our primary or secondary transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

Correction of a mouse model of sickle cell disease: lentiviral/antisickling β-globin gene transduction of unmobilized, purified hematopoietic stem cells

Levasseur

Ryan

Pawlik

et al. 2003

Blood

185

169

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Although sickle cell anemia was the first hereditary disease to be understood at the molecular level, there is still no adequate long-term treatment. Allogeneic bone marrow transplantation is the only available cure, but this procedure is limited to a minority of patients with an available, histocompatible donor. Autologous transplantation of bone marrow stem cells that are transduced with a stably expressed, antisickling globin gene would benefit a majority of patients with sickle cell disease. Therefore, the development of a gene therapy protocol that corrects the disease in an animal model and is directly translatable to human patients is critical. A method is described in which unmobilized, highly purified bone marrow stem cells are transduced with a minimum amount of self-inactivating (SIN) lentiviral vector containing a potent antisickling ␤-globin gene. These cells, which were transduced in the absence of cytokine stimulation, fully reconstitute irradiated recipients and correct the hemolytic anemia and organ pathology that characterize the disease in humans. The mean increase of hemoglobin concentration was 46 g/L (4.6 g/dL) and the average lentiviral copy number was 2.2; therefore, a 21-g/L /vector copy increase (2.1-g/dL) was achieved. This transduction protocol may be directly translatable to patients with sickle cell disease who cannot tolerate current bone marrow mobilization procedures and may not safely be exposed to large viral loads. IntroductionSickle cell disease (SCD) is an autosomal recessive disorder that affects more than 300 000 individuals worldwide and more than 70 000 in the United States. The molecular basis of the disease is an AϾT transversion in the sixth codon of the ␤-globin gene. 1,2 This mutation results in the substitution of a valine residue for glutamic acid on the surface of hemoglobin S (HbS; ␣ 2 ␤ 2 S ) tetramers. The valine creates a hydrophobic projection that fits into a natural hydrophobic pocket formed on hemoglobin tetramers after deoxygenation. 3,4 The interaction of tetramers results in the formation of HbS polymers/fibers that cause red blood cells (RBCs) to become rigid and nondeformable and to occlude small capillaries. 5-10 These vaso-occlusive events cause severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. 11,12 Cycles of erythrocyte sickling also cause the cells to become fragile, and lysis produces chronic anemia. Although sickle cell anemia was the first hereditary disease to be understood at the molecular level, 1,2 there is still no adequate long-term treatment or cure. Current measures focus on induction of fetal hemoglobin to inhibit polymer formation, treatment and prevention of infections, palliative measures to control pain, and surgical treatment of complications. 12 Allogeneic bone marrow transplantation is the only available cure, but this procedure is limited to a minority of patients with an available, histocompatible donor. 13 Autologous trans...

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“…A real opportunity of anti-HBV immunity transfer via donor cells is shown in a study by Lindemann et al [23]. The workers selected a group of patients/matched donor pairs without pre-existing HBV immunity.…”

Section: Vaccine-induced Antibody Response Post-transplantmentioning

confidence: 99%

Time course of immune recovery and viral reactivation following hematopoietic stem cell transplantation

Pankratova¹,

Чухловин²

2016

CTT

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SummaryTotal depletion of innate and adaptive immune cell populations occurs after intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) then followed by gradual recovery of immune populations, due to progenitors derived from donor hematopoietic cells which differentiate to myeloid and lymphoid lineages. Time dynamics of immune reconstitution and differential maturation of distinct immune populations is only partially evaluated, especially, at early terms post-transplant. E.g., innate immunity is restored within 1st month after HSCT, due to rapid reconstitution of granulocytes, monocytes, and natural killer (NK) cells. Meanwhile, functional recovery of mature NK-cell subsets and blood monocytes may continue for up to 3 months.Both T-and B-lymphocyte pools are restored much slower than myelomonocytic populations. The available information on their post-HSCT immune recovery is limited, since most studies are performed at later terms (>1 month post-transplant). Absolute numbers of CD8+ T cells return to control values ca. 4 months post-HSCT, however, exhibiting a skewed repertoire of memory T lymphocytes. Recovery and maturation rates of CD4+ T cells largely depend on residual thymus function, especially, in young subjects. Hence, a naïve CD4+ T cell population in pediatric patients predominates over 6 months post-HSCT. In older persons with inactive thymopoiesis the total CD4 cell counts remain low for years after HSCT. Meanwhile, antiviral cellular immunity is active since early terms post-transplant. E.g., cytotoxic CD8+ cells specific for cytomegalovirus (CMV), or Epstein-Barr virus (EBV) rapidly expand in cases of CMV or EBV activation.Despite recovery of absolute B-cell counts by day 30 post-HSCT, their functions, i.e., antigen-specific antibody production, are reduced for months and years after HSCT, due to slow restoration of mature immune cell populations, thus resemling normal evolution of B cell hierarchy in human organism.Reactivation of herpesviruses (mostly, CMV, EBV and Herpes Simplex) is a known feature of immune deficiency. Timing of maximal herpesvirus incidence (2-3 months post-HSCT) corresponds to the period of CD8+ and CD4+ T cell functional deficiency and B cell immaturity, thus reflecting their suboptimal ability to eliminate herpesvirus-affected leukocytes. Individual terms of immune recovery after allo-HSCT depend on the patients' age, source of donor cells, acute GvHD post-HSCT etc. Vaccination response, being a potent in vivo criterion of immune recovery in post-transplant patients, is also dependent on the subjects' age and restored B cell functions. Time dynamics of specific antibody response shows that the patients with latent CMV reactivation may later exhibit a strong humoral immune response, thus making the infection self-limiting.

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Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation

Abstract: The "spontaneous" recurrence of HBV immunity and the memory response in recipients give evidence for an elective immune transfer (e.g., for viral antigens) by way of allogeneic HCT.

Cited by 38 publications

References 24 publications

Hepatitis B and liver transplantation: 2008 update

Hepatitis B and liver transplantation: 2008 update

Correction of a mouse model of sickle cell disease: lentiviral/antisickling β-globin gene transduction of unmobilized, purified hematopoietic stem cells

Time course of immune recovery and viral reactivation following hematopoietic stem cell transplantation

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