6533b871fe1ef96bd12d1068
RESEARCH PRODUCT
A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses.
Thomas M. KündigWolfgang A. RennerGary T. JenningsFranziska LechnerThomas BächiPeter SebbelPaul PumpensAndrea JegerlehnerIris ErdmannMartin F. BachmannAlain TissotTazio Stornisubject
Models MolecularViral Hepatitis VaccinesHepatitis B virusMacromolecular SubstancesProtein ConformationvirusesRecombinant Fusion ProteinsProtozoan ProteinsAntigens ProtozoanBiologyProtein EngineeringEpitopePhospholipases AInclusion Bodies ViralViral Matrix ProteinsMiceImmune systemAntigenVirus-like particlemedicineAnimalsB cellB-LymphocytesMice Inbred BALB CVaccines SyntheticGeneral VeterinaryGeneral Immunology and MicrobiologyImmunodominant EpitopesImmunogenicityVaccinationPublic Health Environmental and Occupational HealthMolecular biologyHepatitis B Core AntigensPeptide FragmentsCell biologyProtein Structure TertiaryHBcAgBee VenomsInfectious Diseasesmedicine.anatomical_structureCross-Linking ReagentsCapsidDrug DesignMolecular MedicineFemaleImmunizationPeptidesOligopeptidesdescription
Virus like particles (VLPs) are known to induce potent B cell responses in the absence of adjuvants. Moreover, epitope-specific antibody responses may be induced by VLPs that contain peptides inserted in their immunodominant regions. However, due to steric problems, the size of the peptides capable of being incorporated into VLPs while still permitting capsid assembly, is rather limited. While peptides genetically fused to either the N- or C-terminus of VLPs present fewer assembly problems, the immune responses obtained against such epitopes are often limited, most likely because the epitopes are not optimally exposed. In addition, such particles may be less stable in vivo. Here, we show that peptides and proteins engineered to contain a free cys can be chemically coupled to VLPs formed from the hepatitis B core antigen (HBcAg) containing a lys in the immuno-dominant region. By using this approach steric hindrance of capsid assembly is abrogated. Peptides or protein coupled to VLPs in an oriented fashion are shown to induce strong and protective B cell responses even against self-epitopes in the absence of adjuvants. This molecular assembly system may be used to induce strong B cell responses against most antigens.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2002-08-01 | Vaccine |