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      Levamizole enhances immune responsiveness to intra-dermal and intra-muscular hepatitis B vaccination in chronic hemodialysis patients

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      Journal of Immune Based Therapies and Vaccines
      BioMed Central

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          Abstract

          Background

          Hemodialysis patient are at high risk for hepatitis B virus (HBV) infection.

          Although preventive vaccination is done routinely, the response to vaccination is low in this patient population. The aim of this study was to evaluate the effect of Levamizol, an enhancer of the immune responsiveness, on different routs of vaccination, i.e., intradermal (ID) versus intramuscular (IM), in stable chronic hemodialysis patients.

          Materials and methods

          Forty four chronic heamodialyses patient were divided into four equal groups. The first group was received 40 μg HB vaccine intramuscularly. The second group was received 20 μg HB vaccine intradermally. The third and the fourth group received 20 μg vaccine IM or ID, respectively, in three doses plus oral Levamisole (100 mg for 12 day). After one and six months from the last dose of vaccine, HBs antibody titers were measured.

          Results

          The response rate to vaccine (HBs Antibody>10 μg/L) in the routine IM HB vaccination was low (60%). It increased to 70% with ID route. Levamisole significantly raised the response rate to 90% (P < 0.01). Also in the Levamisole groups protective HB antibody titers were maintained until the end of six months.

          We conclude that HD patients must be vaccinated by ID route and addition of Levamisole. Levamisole also increases antibody maintenance.

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          Most cited references38

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          Cellular and humoral immune responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen.

          The vaccination route may influence the success of immunization against pathogens. The conventional intramuscular (i.m.) application of a vaccine containing the hepatitis B virus (HBV) surface antigen (HBsAg) led to protective anti-HBs antibody levels in the majority of vaccine recipients. In this study, we vaccinated healthy volunteers and a group of i.m. vaccine nonresponders via the intradermal (i.d.) route and analyzed the HBV-specific B-cell response as well as class-II- and class-I-restricted T-cell responses by (3)H-thymidine uptake, enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT). The results were then compared with i.m. vaccinated controls. I.d. vaccinations were well tolerated and induced neutralizing anti-HBs antibodies in all naive vaccine recipients and, importantly, all but one former i.m. nonresponder developed protective anti-HBs serum antibody levels after 2 or 3 i.d. immunizations. On the cellular level, i.d. vaccine recipients showed significantly higher anti-HBs producing B-cell frequencies and more vigorous class-II-restricted T-helper (Th) cell responses than i.m. controls. However, although the HBsAg-specific T cells were characterized by their cytokine release as Th1-like cells in both groups, human leukocyte antigen (HLA)-A2+ individuals who received the soluble HBsAg via the i.d. route developed higher peptide-specific cytotoxic CD8+ T cell precursor (CTLp) frequencies. In conclusion, i.d. HBsAg vaccination is more effective even in former i.m. vaccine nonresponders with respect to antibody induction and specific B- and T-cell responses. The induction of virus-specific CTLp may provide the rationale to study the i.d. HBsAg vaccine in the treatment of chronic hepatitis B.
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            The general immunopharmacology of levamisole.

            G Renoux (1980)
            The need for treatments to correct an immunological defect, or to restore an impaired immune response asociated with disease or ageing, has led to the development of nonspecific immunoactive agents. Levamisole, a synthetic low molecular weight compound, is the first member of a new class of drugs which can increase the functions of cellular immunity in normal, healthy laboratory animals. The properties of levamisole have contributed to improved understanding of the molecular events which mediate or trigger immune responses. Levamisole can act either as an immunostimulant agent or an immunosuppressive agent. These apparently paradoxical effects depend upon the dose administered, the timing of its administration, the experimental assay used to measure effects, and the host genetic background. Levamisole's potential for opposite effects explains certain apparent inconsistencies observed in experimental or clinical assays. The drug's actions are modulated by the interaction between the T-cell recruiting efficacy of the sulphur moiety and the cholinergic effects of the imidazole ring. The clinical implications resulting from the immunopharmacological properties of levamisole are obvious: one should avoid its use in diseases without known association with an immune defect, and always attempt to correlate clinical data with modifications of immune parameters, since the therapeutic usefulness of correctly administered levamisole parallels improvement in tests of cellular immunity. Immunomodulators act by modifying the functions of the host cells involved in defences against invaders, and the effectiveness of an immunotherapeutic drug is dependent upon characteristics of the individual host. Thus, therapy with such drugs must be individualised; the appropriate agent and dosage should be chosen according to the immune capabilities of individual patients.
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              Vaccine recommendations for patients on chronic dialysis. The Advisory Committee on Immunization Practices and the American Academy of Pediatrics.

              Pediatric patients on dialysis should receive all the vaccines currently recommended by the ACIP and the AAP for healthy children, except the oral polio vaccine (34, 35). Adult patients should receive the hepatitis B vaccine series, pneumococcal vaccine, yearly influenza vaccinations, tetanus-diphtheria toxoids, and varicella vaccine, if they are susceptible (33, 48, 69). Vaccines are well tolerated by these patients (33), but higher doses and/or additional boosters may be required periodically to adequately protect dialysis patients from vaccine-preventable diseases (33, 36, 37, 82, 83). Following vaccination, antibody concentrations for hepatitis B vaccine should be measured annually and booster doses administered when antibody concentrations fall below protective levels (33, 38). Although both children and adults on dialysis may show an impaired and/or delayed immunologic response to certain antigens, particularly hepatitis B virus and S. pneumoniae, appropriate immunizations can significantly reduce the risk of serious complications from vaccine-preventable diseases (11, 84). Because the protection these vaccines provide may be incomplete or transient, infection control strategies at hospitals and other health care facilities should be implemented simultaneously. Health care providers are encouraged to assess each patients need for vaccinations individually and formulate immunization strategies early in the course of progressive renal disease, ideally before the patient requires dialysis.
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                Author and article information

                Journal
                J Immune Based Ther Vaccines
                Journal of Immune Based Therapies and Vaccines
                BioMed Central (London )
                1476-8518
                2006
                30 May 2006
                : 4
                : 3
                Affiliations
                [1 ]Division of nephrology, Modarres hospital, Shahid beheshti university of medical sciences, Tehran, Iran
                [2 ]Drug applied research center, Tabriz university of medical sciences, Tabriz, Iran
                [3 ]Drug applied research center, Tabriz university of medical sciences, Tabriz, Iran
                Article
                1476-8518-4-3
                10.1186/1476-8518-4-3
                1540413
                16734912
                d56b3400-1685-4db8-8d8c-098534b3d86f
                Copyright © 2006 Hassan and Ebrahim; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 November 2005
                : 30 May 2006
                Categories
                Original Research

                Immunology
                Immunology

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