Versatile virus-like particle carrier for epitope based vaccines.
BACKGROUND
Recombinant proteins and in particular single domains or peptides are often poorly immunogenic unless conjugated to a carrier protein. Virus-like-particles are a very efficient means to confer high immunogenicity to antigens. We report here the development of virus-like-particles (VLPs) derived from the RNA bacteriophage AP205 for epitope-based vaccines.


RESULTS
Peptides of angiotensin II, S.typhi outer membrane protein (D2), CXCR4 receptor, HIV1 Nef, gonadotropin releasing hormone (GnRH), Influenza A M2-protein were fused to either N- or C-terminus of AP205 coat protein. The A205-peptide fusions assembled into VLPs, and peptides displayed on the VLP were highly immunogenic in mice. GnRH fused to the C-terminus of AP205 induced a strong antibody response that inhibited GnRH function in vivo. Exposure of the M2-protein peptide at the N-terminus of AP205 resulted in a strong M2-specific antibody response upon immunization, protecting 100% of mice from a lethal influenza infection.


CONCLUSIONS
AP205 VLPs are therefore a very efficient and new vaccine system, suitable for complex and long epitopes, of up to at least 55 amino acid residues in length. AP205 VLPs confer a high immunogenicity to displayed epitopes, as shown by inhibition of endogenous GnRH and protective immunity against influenza infection.
Tissot
Alain C
AC
Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.
Renhofa
Regina
R
Schmitz
Nicole
N
Cielens
Indulis
I
Meijerink
Edwin
E
Ose
Velta
V
Jennings
Gary T
GT
Saudan
Philippe
P
Pumpens
Paul
P
Bachmann
Martin F
MF
D000818:Animals; D003001:Cloning, Molecular; D000939:Epitopes / Q000737:chemistry*; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012317:RNA Phages / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D014611:Vaccination / Q000295:instrumentation / Q000379:methods; D014771:Virion / Q000737:chemistry*
D000939:Epitopes; D010455:Peptides; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone