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

EBioMedicine. 2016 Sep;11:58-67. doi: 10.1016/j.ebiom.2016.07.023. Epub 2016 Aug 8.


Background: We 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.

Methods: Hepatitis 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.

Findings: IgG 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.

Interpretation: Our 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.

Keywords: Allergy; B cell epitope-based allergy vaccine; Hepatitis B; Hepatitis B surface protein; Virus neutralization; preS.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral
  • Antibody Specificity
  • Disease Models, Animal
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / immunology*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B virus / immunology*
  • Humans
  • Immunization Schedule
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology
  • Immunotherapy* / methods
  • Male
  • Mice
  • Neutralization Tests
  • Pollen / genetics
  • Pollen / immunology*
  • Rabbits
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccination


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Immunoglobulin E