T helper 2 biased <i>de novo</i> immune response to Keyhole Limpet Hemocyanin in humans

Spazierer, Daniel; Skvara, Hans; Dawid, Markus; Fallahi, N.; Gruber, Kristina; Rose, Kadi-Ann; Lloyd, Peter; Heuerding, S.; Stingl, Georg; Jung, Thomas

doi:10.1111/j.1365-2222.2008.03177.x

Cited by 22 publications

(48 citation statements)

References 51 publications

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“…However, alum triggers various side effects like swelling, indurations, erythemas, cutaneous nodules, and granulomas at the injection site [1]. It also favors a Th2-response by inducing undesired production of IgE [2,3]. Therefore, other adjuvants or delivery systems need to be established [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Pali‐Schöll

Szöllösi

Starkl

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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Section: Introductionmentioning

confidence: 99%

Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Pali‐Schöll

Szöllösi

Starkl

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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“…Peripheral blood mononuclear cells (PBMC) isolated from individuals immunized with keyhole limpet hemocyanin (KLH) combined with AH secreted mostly IL-5, IL-10, and IL-13 upon restimulation in vitro and induced IgG1 and IgG4 anti-KLH antibodies consistent with a Th2 response (Spazierer et al, 2009). However, restimulation of PBMC from the same volunteers with tetanus toxoid induced IFN-γ secretion and no IL-13 suggestive of a Th1 response.…”

Section: The Immune Response To Aluminum-adjuvanted Vaccinesmentioning

confidence: 99%

Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants

HogenEsch¹

2013

Front. Immun.

310

281

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Aluminum-containing adjuvants are widely used in preventive vaccines against infectious diseases and in preparations for allergy immunotherapy. The mechanism by which they enhance the immune response remains poorly understood. Aluminum adjuvants selectively stimulate a Th2 immune response upon injection of mice and a mixed response in human beings. They support activation of CD8 T cells, but these cells do not undergo terminal differentiation to cytotoxic T cells. Adsorption of antigens to aluminum adjuvants enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site which allows time for inflammatory cells to accumulate. The adsorptive strength is important as high affinity interactions interfere with the immune response. Adsorption can also affect the physical and chemical stability of antigens. Aluminum adjuvants activate dendritic cells via direct and indirect mechanisms. Phagocytosis of aluminum adjuvants followed by disruption of the phagolysosome activates NLRP3-inflammasomes resulting in the release of active IL-1β and IL-18. Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells. The use of aluminum adjuvant is limited by weak stimulation of cell-mediated immunity. This can be enhanced by addition of other immunomodulatory molecules. Adsorption of these molecules is determined by the same mechanisms that control adsorption of antigens and can affect the efficacy of such combination adjuvants. The widespread use of aluminum adjuvants can be attributed in part to the excellent safety record based on a 70-year history of use. They cause local inflammation at the injection site, but also reduce the severity of systemic and local reactions by binding biologically active molecules in vaccines.

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“…Assays to monitor cellular [25, 26] and humoral [27–29] immune responses against KLH have been developed to facilitate optimal use of biomedical KLH applications. The enzyme-linked immunosorbent assay (ELISA) proved a simple and sensitive assay to measure serological Abs, and in 1979, the first quantitative assay to detect KLH-specific Ab in mice was published [27].…”

Section: Introductionmentioning

confidence: 99%

Humoral anti-KLH responses in cancer patients treated with dendritic cell-based immunotherapy are dictated by different vaccination parameters

Aarntzen

Vries

Goertz

et al. 2012

Cancer Immunol Immunother

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PurposeKeyhole limpet hemocyanin (KLH) attracts biomedical interest because of its remarkable immunostimulatory properties. Currently, KLH is used as vaccine adjuvant, carrier protein for haptens and as local treatment for bladder cancer. Since a quantitative human anti-KLH assay is lacking, it has not been possible to monitor the dynamics of KLH-specific antibody (Ab) responses after in vivo KLH exposure. We designed a quantitative assay to measure KLH-specific Abs in humans and retrospectively studied the relation between vaccination parameters and the vaccine-induced anti-KLH Ab responses.Experimental designAnti-KLH Abs were purified from pooled serum of melanoma patients who have responded to KLH as a vaccine adjuvant. Standard isotype-specific calibration curves were generated to measure KLH-specific Ab responses in individual serum samples using ELISA.ResultsKLH-specific IgM, IgA, IgG and all IgG-subclasses were accurately measured at concentrations as low as 20 μg/ml. The intra- and inter-assay coefficients of variation of this ELISA were below 6.7 and 9.9 %, respectively. Analyses of 128 patients demonstrated that mature DC induced higher levels of KLH-specific IgG compared to immature DC, prior infusion with anti-CD25 abolished IgG and IgM production and patients with locoregional disease developed more robust IgG responses than advanced metastatic melanoma patients.ConclusionsWe present the first quantitative assay to measure KLH-specific Abs in human serum, which now enables monitoring both the dynamics and absolute concentrations of humoral immune responses in individuals exposed to KLH. This assay may provide a valuable biomarker for the immunogenicity and clinical effectiveness of KLH-containing vaccines and therapies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-012-1263-z) contains supplementary material, which is available to authorized users.

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T helper 2 biased de novo immune response to Keyhole Limpet Hemocyanin in humans

Cited by 22 publications

References 51 publications

Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants

Humoral anti-KLH responses in cancer patients treated with dendritic cell-based immunotherapy are dictated by different vaccination parameters

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