A molecular assembly system for presentation of antigens on the surface of HBc virus-like particles.
Hepatitis B virus-like particles, icosahedral structures formed by multiple core protein dimers, are promising immune-enhancing vaccine carriers for foreign antigens. Insertions into the surface-exposed immunodominant loop are especially immunogenic. However, the need to conserve the particulate structure to ensure high immunogenicity imposes restraints on the nature of the heterologous sequence that can be inserted. We propose a new approach to constructing HBc particles linked to the target epitopes that relies on non-covalent interactions between the epitope and pre-assembled unmodified HBc particles. Interaction was enabled by fusion of the epitope to the GSLLGRMKGA peptide, binding to the spike tips. This peptide may be used as a "binding tag" allowing in vitro construction of HBc particles carrying the target peptide. Such virus-like particles carrying multiple copies of the extracellular domain of the M2 protein of different influenza strains appeared to be highly immunogenic and protected immunised mice against a lethal influenza challenge.
Centre Bioengineering, Russian Academy of Sciences, 117312 Prosp. 60-letya Oktyabrya 7-1, Moscow, Russia.
Elena A
EA
Blokhina
Victor V
VV
Kuprianov
Ludmila A
LA
Stepanova
Ludmila M
LM
Tsybalova
Oleg I
OI
Kiselev
Nikolai V
NV
Ravin
Konstantin G
KG
Skryabin
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000939:Epitopes / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000086082:Viroporin Proteins
D000939:Epitopes; D006512:Hepatitis B Core Antigens; D007252:Influenza Vaccines; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C509609:M2e-HBc influenza vaccine