Granulocyte-Macrophage Colony-Stimulating Factor as an Adjuvant to Hepatitis B Vaccination in Maintenance Hemodialysis Patients

U, Anandh; Bastani, Bahar; Ballal, Sudarsham

doi:10.1159/000013556

Cited by 34 publications

(28 citation statements)

References 16 publications

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“…These patients had significantly higher seroprotective titers compared with HBV vaccine alone (p < 0.05). 28 Similarly, in the booster group, GM-CSF adjuvant significantly increased the seroconversion rate (p < 0.02) and showed significantly higher mean anti-HBV titers than the HBV vaccine group (p < 0.05). 28 …”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 82%

“…22 Similarly, in patients with HIV or those on haemodialysis, GM-CSF as an adjuvant administered prior to a primary or booster HBV vaccine dose appears to facilitate greater immunological protection against HBV infection than HBV vaccine alone. 25,27,28 It should be noted that GM-CSF was administered prior to the vaccine, which could complicate compliance in routine immunizations.…”

Section: Discussionmentioning

confidence: 99%

“…In the booster group, patients who had not seroconverted after receiving two doses of HBV vaccine were randomized to receive an additional HBV booster dose or an HBV dose given 24 hours after GM-CSF. 28 In the primary group, more patients were seroprotected with the pre-administration of GMCSF. These patients had significantly higher seroprotective titers compared with HBV vaccine alone (p < 0.05).…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

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Improving vaccine delivery using novel adjuvant systems

Pichichero¹

2008

Human Vaccines

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ASO4, a novel adjuvant, contains aluminum hydroxide and monophosphoryl lipid (MPL) (500 mg aluminum hydroxide and 50 mg 3-O-desacyl-4' MPL A). Aluminum hydroxide is an adjuvant known to facilitate vaccine antigen delivery and transport to the draining lymph nodes by creating a 'depot' at the injection site. 2 Like all aluminum adjuvants, aluminum hydroxide helps improve immunogenicity of low molecular weight antigens, which could otherwise clear rapidly from the injection site or draining lymph nodes. 2 MPL, a non-toxic derivative of lipopolysaccharide, improves specific antibody and cell-mediated immune responses to vaccination. 4 With only minimal toxicity, 5 MPL enhances macrophage and B-and Tcell responses, as well as T-helper cell generation. 5,6 AS04 adjuvant has been shown to improve vaccine-induced immune responses in hepatitis B (HBV) and cervical cancer vaccines.In 2004, Boland et al. 7 described a randomized study where healthy subjects received two doses of HBV vaccine with ASO4 adjuvant or three doses of HBV vaccine with aluminum adjuvant. 7 After the first and second dose of ASO4, substantially more subjects were seropositive for anti-HBV antibodies than after the first and third dose of aluminum adjuvanted vaccine (Table 1). Thus, the ASO4 adjuvant provided the potential for an effective two dose HBV vaccine schedule. In addition, after two doses of ASO4 adjuvanted vaccine, geometric mean titers (GMT) were two times higher than those observed with the aluminum adjuvanted vaccine (7,832 mlU/ml vs 3,725 mlU/ml). No serious adverse events (SAEs) related to the vaccinations occurred, and the overall incidence of vaccine-related adverse events (AEs) (e.g., pain, redness and swelling around the injection site) was comparable between groups. 7 For patients undergoing haemodialysis, the Centers for Disease Control recommends stronger or increased doses of HBV vaccine to assure protective immunity. 8 A clinical trial comparing the immune responses of pre-haemodialysis and haemodialysis patients showed four doses of HBV vaccine was more effective with ASO4 adjuvant than with aluminum adjuvant (Table 1). 9 More patients achieved seroprotection at three months (p = 0.005) and remained seroprotected at 36 months with ASO4 adjuvanted vaccine than with aluminum adjuvanted vaccine (p = 0.03, Table 1). 9 At three and seven months post final dose, signficiantly more patients in the HBV-ASO4 adjuvant group had anti-HB concentrations >100 mlU/mL (p < 0.001 and p < 0.04, respectively), and a higher percentage retained these high anti-HB levels at 36 months

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Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 99%

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Improving vaccine delivery using novel adjuvant systems

Pichichero¹

2008

Human Vaccines

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“…Several previous clinical studies attempted to use GM-CSF as a bolus injection to improve the efficacy of HBsAg vaccine in healthy nonresponders (22) and in hemodialysis patients (23)(24)(25)(26)(27)(28)(29). However, in general, the improvement in vaccine efficacy was not impressive, which might be due to the short serum half-life of GM-CSF (41) and the low local GM-CSF concentration at the point where the immune response was taking place.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, GM-CSF, in the form of a recombinant protein or a gene product encoded by plasmid DNA or viral vectors, has been codelivered as an adjuvant and has proved effective in enhancing immune responses to a number of vaccines (20,21). In terms of HBV vaccines, systemic administration of rGM-CSF was investigated as an adjuvant in healthy nonresponders (22) and in hemodialysis patients (23)(24)(25)(26)(27)(28)(29). However, in these studies, GM-CSF showed no effect or only moderately increased the seroconversion rate and anti-HBs titers.…”

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confidence: 99%

Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells

Chou

Lin

Pan

et al. 2010

The Journal of Immunology

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The standard hepatitis B surface Ag (HBsAg) vaccine fails to induce anti-hepatitis B surface Abs in 5–10% of healthy subjects, a phenomenon known as HBsAg nonresponsiveness, which is closely related to HLA class II alleles and impaired Th cell responses to HBsAg in these subjects. We hypothesized that GM-CSF, a potent adjuvant in enhancing the Ag-presentation activity of APCs, might help to generate Th cell responses in nonresponders, subsequently providing help for B cells to produce anti-hepatitis B surface Abs. We used a thermosensitive biodegradable copolymer (hydrogel) system to codeliver HBsAg and GM-CSF to achieve maximal local cytokine activity at the injection site. In responder mouse strains, hydrogel-formulated HBsAg plus GM-CSF (Gel/HBs+GM) vaccine elicited much greater anti-hepatitis B surface Ab titers and Th cell proliferative responses than a commercial aluminum-formulated HBsAg vaccine or free HBsAg. The adjuvant effect of the Gel/HBs+GM vaccine was dependent upon the local release of GM-CSF. More importantly, the Gel/HBs+GM vaccine elicited high HBsAg-specific Ab titers and Th cell responses in B10.M mice, a mouse strain that does not respond to the current HBsAg vaccine because of its H-2 haplotype. Analysis of the draining lymph nodes of Gel/HBs+GM vaccine-treated mice revealed an elevated number of CD11c+ dendritic cells showing enhanced expression of MHC class II and a variety of costimulatory molecules. These results demonstrate that hydrogel-formulated GM-CSF might represent a simple and effective method to generate next-generation hepatitis B virus vaccines for inducing anti-hepatitis B surface Abs in nonresponders.

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Molecular cloning and expression of woodchuck granulocyte‐macrophage colony stimulating factor*

Chen

Lin

et al. 2001

Journal of Medical Virology

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Granulocyte-macrophage colony stimulating factor (GM-CSF) has immunoregulatory and antiviral effects, and may thus be promising for the treatment of chronic hepatitis B. Using woodchuck hepatitis virus (WHV)-infected woodchuck as an animal model to test the efficacy and safety of GM-CSF on the therapy of chronic hepatitis B, woodchuck GM-CSF will be required due to the apparent species-specific activity of GM-CSF. The cDNA of woodchuck GM-CSF was cloned using reverse transcription-polymerase chain reaction (RT-PCR) with primers deriving from highly conserved regions of GM-CSF genes from other species. The deduced amino acids, including the signal peptide, is 138 in length and its identities to human, murine, canine and bovine GM-CSFs are 63, 49, 63, and 63% respectively. The genomic DNA of woodchuck GM-CSF was also cloned by PCR. Its organization is highly homologous to that of human and murine GM-CSF genes, consisting of four exons and three introns. Cloned woodchuck GM-CSF was expressed transiently in 293T cells. The recombinant protein expressed was found to stimulate the growth and differentiation of woodchuck bone marrow cells, indicating the protein expressed by the cloned gene is functional. These results pave the way for future studies on the potential role of GM-CSF for the treatment of chronic hepatitis B by using this animal model.

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Granulocyte-Macrophage Colony-Stimulating Factor as an Adjuvant to Hepatitis B Vaccination in Maintenance Hemodialysis Patients

Cited by 34 publications

References 16 publications

Improving vaccine delivery using novel adjuvant systems

Improving vaccine delivery using novel adjuvant systems

Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells

Molecular cloning and expression of woodchuck granulocyte‐macrophage colony stimulating factor*

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