Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences 2. Immunogenicity in poor responders to hepatitis B vaccines

Leroux‐Roels, Geert; Desombere, Isabelle; Cobbaut, Luc; Petit, Marie-Anne; Desmons, Pierre; Hauser, P; Delem, A.; Grave, Danny De; Safary, Assad

doi:10.1016/s0264-410x(97)00118-7

Cited by 37 publications

(22 citation statements)

References 21 publications

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“…Studies using overlapping peptides revealed that the pre-S region was important for eliciting T cell responses and, thus, help to improve the immunogenicity of the PreS/S vaccine (60). However, the enhanced immunogenicity was only observed for mammalian cell-produced PreS/S vaccines (57), not for yeastderived PreS/S vaccines (58,59), suggesting that glycosylation might also play a role in the improved immunogenicity. The expected high cost of the mammalian-produced vaccine will limit its clinical application.…”

Section: Discussionmentioning

confidence: 95%

“…HBsAg-pulsed DCs, a cellbased vaccine, was reported to induce anti-HBs Abs in HBsAg vaccine nonresponders (54). The pre-S-containing HBsAg (PreS/ S) vaccine, with addition of the pre-S1 and pre-S2 sequences to the S protein, helped to circumvent immune nonresponsiveness to HBsAg in B10.M mice (55,56) and in several human clinical trials (57)(58)(59). Studies using overlapping peptides revealed that the pre-S region was important for eliciting T cell responses and, thus, help to improve the immunogenicity of the PreS/S vaccine (60).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

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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“…This definition is accepted widely and is based upon the assumption that anti-HBs levels of >10 IU/l are protective [2,[39][40][41][42]. In previous studies [22,29,32], we have observed repeatedly that non/low-responder vaccinees not only display no or a low humoral immune response in vivo, but also fail to mount a lymphoproliferative response upon stimulation with HBsAg in vitro. This correlation between in vivo humoral and in vitro cellular responses suggests that the inadequate antiHBs production in vivo (non-responsiveness) may be due to a lack of T cell help.…”

Section: Discussionmentioning

confidence: 99%

“…For the B7-co-stimulation analysis, two poor-responder (NR1 and NR46) and four HR vaccinees (R15, R17, R21 and R135) were selected from previous vaccination studies [22,29,32]. The HBsAg-presentation capacity of NR1, a DR7-homozygous individual, has been demonstrated previously [24].…”

Section: Subjectsmentioning

confidence: 99%

“…Five HLA-DR0301 + NR to the HB vaccine (NR14, NR24, NR34, NR46 and NR60), all negative for HBsAg, antibodies to hepatitis B core antigen (anti-HBc) and HBV-DNA, were selected from a vaccination study [29] wherein 46 NR were revaccinated with three or four supplementary doses given at monthly intervals of a recombinant hepatitis B vaccine (Engerix-B ® ) [30] or an experimental hepatitis B vaccine (SL*) [31] (both manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium).…”

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confidence: 99%

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Non-responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation

Desombere

Cao

Gijbels

et al. 2005

Clinical and Experimental Immunology

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SummaryThe mechanisms causing non-responsiveness to hepatitis B surface antigen (HBsAg) vaccines in man remain elusive. The increased incidence of nonresponsiveness in subjects with HLA-DR3 + + + + NR were able to present HBsAg. In the present paper we demonstrate that six DR0301 + + + + NR, five of which are homozygous for this marker, were able to take up, process and present HBsAg to HBsAg-specific, DR0301-restricted T cell lines. Non-fractionated peripheral blood mononuclear cells (PBMC) from the DR0301 + + + + NR did not proliferate to HBsAg in vitro , whereas they proliferated vigorously upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. We therefore conclude that HLA-DR0301 + + + + NR vaccinees are not deficient in their HBsAgpresentation. Because it was demonstrated that recently activated T cells can apparently bypass the requirement for B7, we may have overlooked the role of the B7-co-stimulation in our set-up that used HBsAg-specific T cell lines. Therefore we examined the expression of B7 co-stimulatory molecules on NR-APC. CD86 was normally present on these cells and was not down-regulated after culturing the PBMC in the presence of HBsAg. We conclude that CD86 expression on CD14 + + + + monocytes of DR0301-and DR07-homozygous poor responders is not deficient and cannot be the mechanism underlying the nonresponsiveness of these subjects.Keywords: antigen presentation, DRB1*0301, HBsAg, hepatitis B vaccines, non-response I ntroductionFor nearly two decades, vaccines against hepatitis B virus (HBV) have been administered routinely and the antibodies to the hepatitis B surface antigen (HBsAg) they elicit are clearly effective in preventing infections with HBV. About 5% of healthy vaccine recipients fail to produce protective levels of antibodies (defined as an antibody level £ 10 IU/l) to the hepatitis B vaccine after standard immunization. This phenomenon has been observed in all surveys of vaccine effectiveness, irrespective of the HBsAg vaccine employed [1][2][3], and its cause remains largely unknown.Variations in immune response are often associated with polymorphism of the major histocompatibility complex (MHC). The suggestion that MHC-linked immune response genes may control the human response to HBsAg was first made in 1981 by Walker et al . [4], who observed a significant excess of HLA-DR7 and a total absence of HLA-DR1 in hepatitis B non-responders (NR). Subsequent studies demonstrated that HLA class II alleles that are associated strongly with high response (or protect from non/poor response) are: DRB1*01 ( DR1 ), DRB1*11 ( DR5 ), DRB1*15 ( DR2 ), DQB1*0501, DPB1*0401, whereas alleles strongly associated with non/poor response are: DRB1*03, DRB1*07, DQB1*02, ,9,13-18] and, in particular, homozygotes for these extended haplotypes were seen more frequently [1,19,20]. In our studies, for example, six of seven DRB1*07 homozygous individuals and five of six DRB1*0301 homozygous individuals were found to be NR.We and other groups have reported t...

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New Vaccine Technologies and the Control of Viral Hepatitis

Howard¹

2005

Viral Hepatitis

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Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences 2. Immunogenicity in poor responders to hepatitis B vaccines

Cited by 37 publications

References 21 publications

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

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

Non-responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation

New Vaccine Technologies and the Control of Viral Hepatitis

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