Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines

Leroux‐Roels, Geert; Vanhecke, Elsa; Michielsen, Walter; Voet, Pierre; Hauser, P; Pêtre, J

doi:10.1016/0264-410x(94)90290-9

Cited by 58 publications

(40 citation statements)

References 23 publications

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“…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 that subjects displaying a low or no antibody response to HBsAg also failed to mount an efficient HBsAg-specific T helper (Th) cell response in vitro [21,22]. MHC class II molecules mediate Th cell activation by binding peptides, known as T cell epitopes, and presenting these MHC-peptide complexes on the surface of antigen presenting cells (APC) to Th cells.…”

mentioning

confidence: 45%

“…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%

“…The in vitro cellular immune response of the vaccinees was measured using a HBsAg-specific lymphocyte proliferation assay (LPA) as described in a previous paper [22]. Nonfractionated PBMC were suspended in RPMI-1640 medium supplemented with 25 m m Hepes, 50 U/ml penicillin, 50 m g/ ml streptomycin, 2 m m l -glutamine (all from Invitrogen Corporation, Carlsbad, CA, USA), 5 ¥ 10 -5 m 2-ME (Sigma Chemical Co., St Louis, MO, USA) and 10% heat-inactivated human AB + serum (complete medium).…”

Section: Lymphoproliferation Assaysmentioning

confidence: 99%

“…We and other groups have reported that subjects displaying a low or no antibody response to HBsAg also failed to mount an efficient HBsAg-specific T helper (Th) cell response in vitro [21,22]. MHC class II molecules mediate Th cell activation by binding peptides, known as T cell epitopes, and presenting these MHC-peptide complexes on the surface of antigen presenting cells (APC) to Th cells.…”

Section: Introductionmentioning

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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mentioning

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Lymphoproliferation Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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In vitro use of autologous dendritic cells improves detection of T cell responses to hepatitis B virus (HBV) antigens

Carotenuto

Artsen

Niesters

et al. 2008

Journal of Medical Virology

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T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are vigorous and easily detectable in vitro during recovery from acute hepatitis B but significantly weaker in patients with chronic HBV infection. In contrast, T cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable during infection and even in a substantial fraction of subjects receiving vaccination with HBsAg. The aim of this study was to investigate whether the use of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV-specific T cells in these conditions. Autologous monocyte-derived DCs, compared to direct HBsAg addition to the cultures, increased the stimulation of HBs- specific T cells. These were detected in 73% of healthy subjects who had recently received hepatitis B vaccine and in 43% of patients recovering from acute hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis B patients. A longitudinal evaluation of HBc-specific T cell responses during and after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc-specific CD4(+) T cell responses had no correlation with sustained virus suppression whereas CD8(+) T cell responses were more frequently detected in patients able to control HBV replication after therapy interruption. The use of autologous DCs as antigen-presenting cells appears applicable to clinically relevant in vitro evaluation of T cell responses, particularly in those conditions characterized by low frequency of circulating antigen-specific cells and suboptimal in vivo activation.

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Role of G Protein β3 Subunit C825T and HLA Class II Polymorphisms in the Immune Response after HBV Vaccination

et al. 2002

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The G protein beta3 (GNB3) subunit and HLA are candidate genes predictive of immune response capacity. We therefore studied the influence of both gene systems on cellular and humoral immunity against hepatitis B virus (HBV) in 79 HBV booster-vaccinated healthy volunteers and an independent group of 77 probands after HBV basic immunization. Following booster vaccination, lymphocyte in vitro proliferation after stimulation with HBV surface antigen was 2.5-fold increased in GNB3 825T (TC + TT) vs CC allele carriers (P = 0.01) and was not influenced by HLA-DRB1 or DQB1 alleles. In addition, anti-HBs antibody titers in both groups were 2-fold increased in TC vs CC and decreased in TT vs CC allele carriers. However, antibody titers after HBV booster immunization were elevated in HLA-DQB1*0301 carriers (P corrected = 0.027). In summary, the GNB3 825T allele appears as a marker particularly predictive of cellular and HLA-DQB1*0301 of humoral immune responses following HBV vaccination.

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Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen (HBsAg) vaccines

Cited by 58 publications

References 23 publications

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

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

In vitro use of autologous dendritic cells improves detection of T cell responses to hepatitis B virus (HBV) antigens

Role of G Protein β3 Subunit C825T and HLA Class II Polymorphisms in the Immune Response after HBV Vaccination

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