Optimisation of secretion of recombinant HBsAg virus-like particles: Impact on the development of HIV-1/HBV bivalent vaccines. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Vaccine Année : 2007

Optimisation of secretion of recombinant HBsAg virus-like particles: Impact on the development of HIV-1/HBV bivalent vaccines.

Marie Michel
  • Fonction : Auteur
Yu-Chun Lone
  • Fonction : Auteur
Mireille Centlivre
Simon Wain-Hobson
  • Fonction : Auteur
  • PersonId : 858308

Résumé

The hepatitis B surface antigen (HBsAg) assembles into virus-like particles (VLPs) that can be used as carrier of immunogenic peptides for the development of bivalent vaccine candidates. It is shown here that by respecting certain qualitative features of mammalian preS1 and preS2 protein domains upstream of HBsAg, foreign sequences can be inserted in their place while maintaining efficient secretion of VLPs. A polyepitope bearing HIV-1 epitopes restricted to the HLA-A*0201 class I allele was optimised for secretion as an HBsAg fusion protein by counterbalancing the generally hydrophobic class I epitopes with hydrophilic spacers, eliminating epitopes bearing cysteine residues, limiting the number of internal methionine residues to a minimum and adopting Homo sapiens codon usage. The optimised HIV-1 polyepitope-HBsAg recombinant protein with up to 138 residues assembled into efficiently secreted recombinant VLPs. DNA immunisation in HLA-A*0201 and HLA-A*0201/HLA-DR1 transgenic mice resulted in the recovery of humoral response against the carrier and enhanced levels of HIV-1 specific CD8(+) T lymphocyte activation. Efficient self-assembly of recombinant HBsAg VLPs opens up the possibility of making efficient bivalent HBV/HIV vaccine candidates, which is particularly apposite given that the two viruses are frequently associated.

Domaines

Virologie

Dates et versions

hal-00167787 , version 1 (23-08-2007)

Identifiants

Citer

Marie Michel, Yu-Chun Lone, Mireille Centlivre, Pascal Roux, Simon Wain-Hobson, et al.. Optimisation of secretion of recombinant HBsAg virus-like particles: Impact on the development of HIV-1/HBV bivalent vaccines.. Vaccine, 2007, 25 (10), pp.1901-11. ⟨10.1016/j.vaccine.2006.08.014⟩. ⟨hal-00167787⟩

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