Virus-like particles-universal molecular toolboxes - PubMed (original) (raw)

Review

Virus-like particles-universal molecular toolboxes

Christine Ludwig et al. Curr Opin Biotechnol. 2007 Dec.

Abstract

Virus-like particles (VLPs) are highly organised spheres that self-assemble from virus-derived structural antigens. These stable and versatile subviral particles possess excellent adjuvant properties capable of inducing innate and cognate immune responses. Commercialised VLP-based vaccines have been successful in protecting humans from hepatitis B virus (HBV) and human papillomavirus (HPV) infection and are currently explored for their potential to combat other infectious diseases and cancer. Much insight into VLP-mediated immune stimulation and optimised VLP design has been gained from human immunodeficiency virus (HIV)-derived VLPs presenting promising components of current AIDS vaccine approaches. Owing to their unique features, VLPs and virosomes, the in vitro-reconstituted VLP counterparts, have recently gained ground in the field of nanobiotechnology as organic templates for the development of new biomaterials.

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Figures

Figure 1

Figure 1

VLP-based strategies for vaccine design. (A) Schematic presentation of a virus-like particle composed of self-assembled virus capsid proteins that are engulfed by a host cell-derived lipid membrane with integrated cellular proteins; random packaging of cellular nucleic acids is indicated. (B) Vector constructs used to express chimeric HIV VLPs; top: VLPs assembled from Gag or Gag-Pol proteins present endogenous (hatched box) epitopes; additional foreign epitopes can either be inserted or fused (yellow box); middle: VLP-display of incorporated envelope proteins by co-expression of either autologous (gp120/gp41) or heterologous (e.g. gp64) envelopes, the latter resulting in pseudotyping; bottom: co-stimulatory molecules (CD40L) can be anchored on VLPs via a transmembrane domain (TM); Cy, cytoplasmic domain. (C) Production of VLPs in different expression systems. Left: infection of HighFive™ insect cells with recombinant baculoviruses (BV) expressing respective capsid proteins; VLPs budding from insect cells (electron microscopy images) carry BV gp64; right: co-transfection of mammalian 293 T cells with a gag encoding plasmid; co-expression of gp64 results in pseudotyping of Gag VLPs. P CMV, cytomegalovirus promoter; P SV40, Simian virus 40 promoter.

Figure 2

Figure 2

Putative mechanisms of VLP-mediated stimulation of innate and cognate immune responses. (A) Model for the activation of dendritic cells (DCs) by baculo-derived VLP preparations. VLPs are taken up by DCs via endocytosis (1) directing antigen processing in late endosomes (LE) and presentation via the MHC class-II pathway (red path), or via receptor (R)-mediated fusion triggered by gp64 (2a) resulting in proteasomal antigen processing in the cytoplasm and subsequent presentation on MHC class-II (blue path). Baculoviruses (BV) are taken up by gp64-mediated fusion (2b). Danger signals from CpG-rich BV-DNA are recognised by endosomal (E) Toll like receptor 9 (TLR9) and transmitted via a MyD88-dependent (a) or independent (b) signalling pathway resulting in activation of transcription (Tk) and production of inflammatory cytokines and type 1 interferons. A TLR9-independent route of DNA recognition inducing production of IFN-α has also been described (c). Additionally, BV-derived components other than DNA might contribute to DC activation (d). G, Golgi; ER, endoplasmic reticulum; NC, nucleus; P, proteasome; TV, transport vesicle. (B) VLP-mediated maturation of DCs. Uptake of VLP/BV activates DC via danger signals resulting in upregulation of DC maturation markers. Mature DCs present VLP-derived antigens to naive CD4+ and CD8+ T cells via MHC class-I and class-II. Secretion of cytokines by DCs stimulates differentiation into B and T effector cells resulting in antibody release and cytotoxic T cell (CTL) responses.

References

    1. Bayer M.E., Blumberg B.S., Werner B. Particles associated with Australia antigen in the sera of patients with leukaemia, Down's Syndrome and hepatitis. Nature. 1968;218:1057–1059. - PubMed
    1. Blumberg B.S., Millman I., London W.T. Ted Slavin's blood and the development of HBV vaccine. N Engl J Med. 1985;312:189. - PubMed
    1. Doan L.X., Li M., Chen C., Yao Q. Virus-like particles as HIV-1 vaccines. Rev Med Virol. 2005;15:75–88. Review. - PubMed
    1. Young K.R., McBurney S.P., Karkhanis L.U., Ross T.M. Virus-like particles: designing an effective AIDS vaccine. Methods. 2006;40:98–117. Review. - PubMed
    1. McAleer W.J., Buynak E.B., Maigetter R.Z., Wampler D.E., Miller W.J., Hilleman M.R. Human hepatitis B vaccine from recombinant yeast. Nature. 1984;307:178–180. - PubMed

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