Immune response to hepatitis B vaccine in HIV-infected subjects using granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant: ACTG study 5220

Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO 63110, USA.
Vaccine (Impact Factor: 3.62). 08/2010; 28(34):5597-604. DOI: 10.1016/j.vaccine.2010.06.030
Source: PubMed


HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open-label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals >or=18 years of age, CD4 count >or=200 cells/mm(3), seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm(3), 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF arm reported transient grade >or=2 signs/symptoms (six grade 2, one grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb >or=10 mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF vs. control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 >or=350 cells/mm(3) (64%) than with CD4 <350 cells/mm(3) (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted.

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Available from: Debra DeMarco Shaw, Oct 02, 2015
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    • "timulatory molecules on the surfaces of antigen presenting cells ( APCs ) ( Zecher et al . , 1993 ) . More importantly , the majority of the preclinical and clinical data demonstrate low toxicity profiles of GM - CSF in a variety of vaccine approaches in mice and humans , including recombinant vector vaccines , viral vaccines and DNA vac - cines ( Overton et al . , 2010 ; Staff et al . , 2011 ; Wang et al . , 2009 ) . Since PRRSV has the ability to escape from or modulate the host immune system and appears to evolve rapidly , none of the cur - rent PRRSV vaccines can fully eradicate the disease ( Darwich et al . , 2010 ) . Reverse genetics is the most powerful genetic tool in mod - ern virology for use"
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    ABSTRACT: Porcine reproductive and respiratory syndrome virus (PRRSV) has spread worldwide, causing huge economic losses to the swine industry. The current PRRSV vaccines have failed to provide broad protection against various strains. Granulocyte macrophage colony-stimulating factor (GM-CSF), an efficacious adjuvant, has been shown to enhance the immunogenicity of various vaccines. The purpose of this study was to construct a recombinant live attenuated PRRSV that expresses porcine GM-CSF (pGM-CSF) and evaluate the immune responses of pigs immunized with the recombinant virus. The results showed that the recombinant PRRSV was successfully rescued and had similar growth properties to parental virus grown in Marc-145 cells. The recombinant virus was stable for 10 passages in cell culture. Pigs intramuscularly immunized with the recombinant virus produced a similar humoral response to that elicited using parental virus. With regard to cell-mediated immunity assessed in peripheral blood, the recombinant virus induced higher proportion of CD4(+)CD8(+) double-positive T cells (DPT), higher IFN-γ level at 0 and 7 days post-challenge (DPC), and lower viremia at 21 DPC than pigs immunized with parental virus. These results indicate that recombinant PRRSV expressing pGM-CSF can induce a significant higher cellular immune response and reduce the persistent infection compared pigs vaccinated with the parental virus. This is first report of evaluation of immune response in pigs elicited by a recombinant live attenuated PRRSV expressing porcine GM-CSF. It may represent a novel strategy for future development of genetic engineered vaccines against PRRSV infection. Copyright © 2015 Elsevier B.V. All rights reserved.
    Veterinary Immunology and Immunopathology 08/2015; DOI:10.1016/j.vetimm.2015.08.003 · 1.54 Impact Factor
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    • "Liver-related mortality rates of patients with both HBV and HIV infections show a 10-15 fold increase compared with those with only one of these infections. Also, it has been observed that HIV infected patients who have previously been infected with HBV were more likely to develop chronic disease (4, 5) which can result in; cirrhosis, hepatic failure and development of hepatocellular carcinoma (3, 6). Therefore, prevention of hepatitis B in HIV infected patients plays an important role in improving the quality and quantity of their lives. "
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    ABSTRACT: Human immunodeficiency virus (HIV) infected patients are also frequently exposed to the hepatitis B virus (HBV), due to the common routes of transmission, therefore, prevention of hepatitis B results in decreased complications of the disease. Since the immune response of HIV patients to hepatitis B vaccination is less robust than that found in healthy individuals, this study aimed to evaluate the effect of a levamisole adjuvant on increasing the immune response. In this study, 89 HIV infected patients, without a history of HBV infection or vaccination, were randomly allocated into experimental (44 patients) and control (45 patients) groups. HBV vaccination was performed using the Hepavax-Gene TF vaccine, 40 μg three times at intervals of; zero, one, and three months. Levamisole 50 mg twice a day or a placebo, was administered to the experimental and control groups, respectively, for a period of six days before to six days after the vaccination. Immune response was evaluated by measuring hepatitis B surface antibodies (HBsAb) concurrently with the second and third vaccine administration, and at one and three months at the conclusion of the vaccination program. The immune response following the threevaccinations was higher in those who were receiving levamisole compared with the controls (90% vs. 65.38%) (P = 0.05). Furthermore, the immune response and the mean antibody titer following the repeated vaccination in the experimental group showed a higher increase than in the control group. The immune response and the mean titer of antibody were not associated with; age, sex, body mass index, history of smoking and/or intravenous drug use in either of the groups. However, regarding CD4+ cells more than 200 cell/mm3, mean antibody production significantly increased in both groups. Using levamisole with the hepatitis B vaccination can increase the immune response and antibody titer mean in HIV infected patients. Since these patients have a more complete response with CD4+ cells more than 200 cell/mm3, vaccination and effective adjuvants seem to be most beneficial when CD4+ cells are greater than 200 cell/mm3, in HIV infected patients.
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