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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    • "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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    • "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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