Virus‐Like Particles: Combining Innate and Adaptive Immunity for Effective Vaccination

Efficient disulfide bond formation in virus-like particles

“…The truncated HBc VLP monomer reportedly results in predominantly a 240mer VLP while the full length HBc VLP monomer is dimorphic and assembles into both a 240mer and a 180mer VLP (Scheme 2C) (Zlotnick et al, 1996). The HBc VLP with disulfide bonds is of interest due to its increased stability (Table 1) and projecting alpha helix clusters which are attractive sites for attachment of small molecules or the display of fusion protein segments (Bachman and Jennings, 2004;Lechner et al, 2002;Stahl and Murray, 1989). The SS-MS2 VLP is assembled from a rationally designed mutant (C46A, T65C, G73C) of the MS2 coat protein (Scheme 2A).…”

Escherichia coli‐based cell‐free synthesis of virus‐like particles

“…While VLP can serve as excellent vaccines against the virus from which they originated, VLP can also serve as vaccine-templates against virtually any disease by surface presentation of exogenous antigens. Although initial attempts to present foreign epitopes fused into the capsid proteins was largely unsuccessful, attachment by chemical linkage to exposed amino acids has been successfully demonstrated for a number of different ligands (Bachmann and Jennings, 2004;Kratz et al, 1999). Examples of ligands attached to the surface of VLP using this technique include: fluorophores (Peabody, 2003), antibodies (Brown et al, 2002), ligands for cell-specific receptor-mediated endocytosis (Wu et al, 1995), poly(ethylene glycol) (Brown et al, 2002), and immunogens for vaccines (Lechner et al, 2002).…”

“…These VLP are of great interest for vaccination as they: (1) stimulate strong T cell and B cell responses, due to their repeated and ordered surface (Bachmann and Jennings, 2004), (2) do not cause infection, as they are genome-free, (3) have a long serum half-life due to their size and stability, and (4) are the perfect size for uptake into lymphatic vessels for recognition by the immune system (Reddy et al, 2006). The FDA approved human Papillomavirus vaccine and the human Hepatitis B vaccines are two examples of VLP-based vaccines.…”

EDiP: the Epitope Dilution Phenomenon. Lessons learnt from a malaria vaccine antigen and its applicability to polymorphic antigens

“…It is assumed that the antigen in this highly organized repetitive form can more efficiently trigger B cells [47][48][49]. Indeed, this type of antigen may need to be presented in a multimeric form, on a single particle, to be able to trigger B cells capable of mounting broadly neutralizing responses.…”

“…Indeed, this type of antigen may need to be presented in a multimeric form, on a single particle, to be able to trigger B cells capable of mounting broadly neutralizing responses. Such VLPs are expected to be able to activate B-cells capable of producing broadly neutralizing influenza antibodies [47,48]. VLPs expressing multiple HA molecules (H2, H5, H7 or H1, H3 and B) on the same particle have been produced and shown to be immunogenic [50], and the presentation of multiple molecules on a single particle will be highly cost-effective.…”