title: A Fusion Protein Consisting of the Vaccine Adjuvant Monophosphoryl Lipid A and the Allergen Ovalbumin Boosts Allergen-Specific Th1, Th2, and Th17 Responses In Vitro.
abstract: Background. The detoxified TLR4-ligand Monophosphoryl Lipid A (MPLA) is the first approved TLR-agonist used as adjuvant in licensed vaccines but has not yet been explored as part of conjugated vaccines. Objective. To investigate the immune-modulating properties of a fusion protein consisting of MPLA and Ovalbumin (MPLA : Ova). Results. MPLA and Ova were chemically coupled by stable carbamate linkage. MPLA : Ova was highly pure without detectable product-related impurities by either noncoupled MPLA or Ova. Light scattering analysis revealed MPLA : Ova to be aggregated. Stimulation of mDC and mDC : DO11.10 CD4(+) TC cocultures showed a stronger activation of both mDC and Ova-specific DO11.10 CD4(+) TC by MPLA : Ova compared to the mixture of both components. MPLA : Ova induced both strong proinflammatory (IL-1β, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokine responses from mDCs while also boosting allergen-specific Th1, Th2, and Th17 cytokine secretion. Conclusion. Conjugation of MPLA and antigen enhanced the immune response compared to the mixture of both components. Due to the nonbiased boost of Ova-specific Th2 and Th17 responses while also inducing Th1 responses, this fusion protein may not be a suitable vaccine candidate for allergy treatment but may hold potential for the treatment of other diseases that require a strong stimulation of the host's immune system (e.g., cancer).
authors.affiliation: Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Hessen, Germany.
authors.forename: Stefan
authors.identifier: 0000-0002-9674-5116
authors.initials: S
authors.lastname: Schülke
authors.affiliation: Division of Allergology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Vogel
authors.affiliation: Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Hessen, Germany.
authors.forename: Ann-Christine
authors.identifier: 0000-0001-7600-4639
authors.initials: AC
authors.lastname: Junker
authors.affiliation: Division of Microbiology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
authors.forename: Kay-Martin
authors.initials: KM
authors.lastname: Hanschmann
authors.affiliation: Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Hessen, Germany.
authors.forename: Adam
authors.identifier: 0000-0002-9799-3170
authors.initials: A
authors.lastname: Flaczyk
authors.affiliation: Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Hessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vieths
authors.affiliation: Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Hessen, Germany.
authors.forename: Stephan
authors.identifier: 0000-0002-2859-562X
authors.initials: S
authors.lastname: Scheurer
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D016207:Cytokines; D008050:Lipid A; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D010047:Ovalbumin; C048436:monophosphoryl lipid A