title: Mechanisms, safety and efficacy of a B cell epitope-based vaccine for immunotherapy of grass pollen allergy.
abstract: BACKGROUND
  We have developed a recombinant B cell epitope-based vaccine (BM32) for allergen-specific immunotherapy (AIT) of grass pollen allergy. The vaccine contains recombinant fusion proteins consisting of allergen-derived peptides and the hepatitis B surface protein domain preS as immunological carrier.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled AIT study to determine safety, clinical efficacy and immunological mechanism of three subcutaneous injections of three BM32 doses adsorbed to aluminum hydroxide versus aluminum hydroxide (placebo) applied monthly to grass pollen allergic patients (n=70). Primary efficacy endpoint was the difference in total nasal symptom score (TNSS) through grass pollen chamber exposure before treatment and 4weeks after the last injection. Secondary clinical endpoints were total ocular symptom score (TOSS) and allergen-specific skin response evaluated by titrated skin prick testing (SPT) at the same time points. Treatment-related side effects were evaluated as safety endpoints. Changes in allergen-specific antibody, cellular and cytokine responses were measured in patients before and after treatment.
  
  
  RESULTS
  Sixty-eight patients completed the trial. TNSS significantly decreased with mean changes of -1.41 (BM32/20μg) (P=0.03) and -1.34 (BM32/40μg) (P=0.003) whereas mean changes in the BM32/10μg and placebo group were not significant. TOSS and SPT reactions showed a dose-dependent decrease. No systemic immediate type side effects were observed. Only few grade 1 systemic late phase reactions occurred in BM32 treated patients. The number of local injection site reactions was similar in actively and placebo-treated patients. BM32 induced highly significant allergen-specific IgG responses (P<0.0001) but no allergen-specific IgE. Allergen-induced basophil activation was reduced in BM32 treated patients and addition of therapy-induced IgG significantly suppressed T cell activation (P=0.0063).
  
  
  CONCLUSIONS
  The B cell epitope-based recombinant grass pollen allergy vaccine BM32 is well tolerated and few doses are sufficient to suppress immediate allergic reactions as well as allergen-specific T cell responses via a selective induction of allergen-specific IgG antibodies. (ClinicalTrials.gov number, NCT01445002.).
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Zieglmayer
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Margarete
authors.initials: M
authors.lastname: Focke-Tejkl
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Schmutz
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lemell
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Zieglmayer
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Milena
authors.initials: M
authors.lastname: Weber
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Renata
authors.initials: R
authors.lastname: Kiss
authors.affiliation: Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: BIOMAY AG, Vienna, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Stolz
authors.affiliation: BIOMAY AG, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Huber
authors.affiliation: BIOMAY AG, Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: SynteractHCR, Munich, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Knoll
authors.affiliation: Vienna Challenge Chamber, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Horak
authors.affiliation: BIOMAY AG, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Henning
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: Rudolf.valenta@meduniwien.ac.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000328:Adult; D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D006109:Poaceae / Q000009:adverse effects*; D011058:Pollen / Q000276:immunology*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D007073:Immunoglobulin E
keywords: B cell-epitope; Challenge chamber; Grass pollen; Immunotherapy; Vaccine