Versatile Virus-Like Particle Carrier for Epitope Based Vaccines |
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Authors: | Alain C. Tissot Regina Renhofa Nicole Schmitz Indulis Cielens Edwin Meijerink Velta Ose Gary T. Jennings Philippe Saudan Paul Pumpens Martin F. Bachmann |
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Affiliation: | 1. Cytos Biotechnology AG, Zurich-Schlieren, Switzerland.; 2. Latvian Biomedical Research and Study Centre, Riga, Latvia.;Instituto Butantan, Brazil |
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Abstract: | BackgroundRecombinant 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.Methodology/Principal FindingsPeptides 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/SignificanceAP205 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. |
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