Immunotherapy With the PreS-based Grass Pollen Allergy Vaccine BM32 Induces Antibody Responses Protecting Against Hepatitis B Infection

Abstract

BackgroundWe have constructed and clinically evaluated a hypoallergenic vaccine for grass pollen allergy, BM32, which is based on fusion proteins consisting of peptides from the IgE binding sites of the major grass pollen allergens fused to preS (preS1 + preS2), a domain of the hepatitis B virus (HBV) large envelope protein which mediates the viral attachment and entry. Aim of this study was the characterization of the HBV-specific immune response induced by vaccination of allergic patients with BM32 and the investigation of the vaccines' potential to protect against infection with HBV.MethodsHepatitis B-specific antibody and T cell responses of patients vaccinated with BM32 were studied using recombinant preS and synthetic overlapping peptides spanning the preS sequence. The specificities of the antibody responses were compared with those of patients with chronic HBV infection. Furthermore, the capacity of BM32-induced antibodies, to inhibit HBV infection was investigated using HepG2-hNTCP cell-based in vitro virus neutralization assays.FindingsIgG antibodies from BM32-vaccinated but not of HBV-infected individuals recognized the sequence motif implicated in NTCP (sodium-taurocholate co-transporting polypeptide)-receptor interaction of the hepatitis B virus and inhibited HBV infection.InterpretationOur study demonstrates that the recombinant hypoallergenic grass pollen allergy vaccine BM32 induces hepatitis B-specific immune responses which protect against hepatitis B virus infection in vitro.

Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE cross‐reactivity

“…Second and most important, our study has mapped the major IgE epitope‐containing areas of Der p 5 and Der p 21 and we could identify nonallergenic peptides from these areas which can be used for the construction of allergy vaccines based on carrier‐bound B cell epitopes . A vaccine based on nonallergenic B cell epitope‐derived peptides of the four major timothy grass pollen allergens has in fact been described and was shown to be clinically effective in immunotherapy trials in grass pollen‐allergic patients . Our work therefore will be important for the rational engineering of a recombinant vaccine for the treatment of HDM allergy.…”

Novel approaches and perspectives in allergen immunotherapy

“…Recombinant allergens may also be genetically modified to reduce IgE binding and allergenicity with great potential for safer immunotherapy. The recombinant vaccine protein BM32, encompassing non‐IgE binding domains from grass allergens Phl p 1, 2, 5 and 6 fused with a hepatitis B viral surface protein, is currently in phase 2 studies . Patients treated with this vaccine raised IgG antibody to allergens and hepatitis B viral sequences encoded by the recombinant proteins.…”

“…Patients treated with this vaccine raised IgG antibody to allergens and hepatitis B viral sequences encoded by the recombinant proteins. The immune response to both allergen and virus was protective in vitro , and patients had reduced allergy symptoms in an AEC challenge . Recombinant approaches may ultimately allow tailor‐made immunotherapy for individuals , which will not induce novel sensitizations to irrelevant allergens found in extracts.…”

Next generation immunotherapy for tree pollen allergies

“…81 Alternatively, the chemical coupling was replaced by recombinant fusion protein consisting of a viral protein as a carrier such as the VP1 from human rhinovirus or the protein PreS domain from hepatitis B virus and the B-cell epitopes. 80,[83][84][85] Without a secondary structure, these B cell epitopes neither recognize IgE antibodies from birch allergenic patients nor induce basophil activation and skin test reactions. In animal models, these B-cell epitopes induced functional allergenspecific IgG antibodies, which exhibited IgE blocking activity as indicated by inhibition of IgE binding to serum from allergic patients and by blocking basophil activation by allergens.…”