title: A microbial platform for rapid and low-cost virus-like particle and capsomere vaccines.
abstract: Studies on a platform technology able to deliver low-cost viral capsomeres and virus-like particles are described. The technology involves expression of the VP1 structural protein from murine polyomavirus (MuPyV) in Escherichia coli, followed by purification using scaleable units and optional cell-free VLP assembly. Two insertion sites on the surface of MuPyV VP1 are exploited for the presentation of the M2e antigen from influenza and the J8 peptide from Group A Streptococcus (GAS). Results from testing on mice following subcutaneous administration demonstrate that VLPs are self adjuvating, that adding adjuvant to VLPs provides no significant benefit in terms of antibody titre, and that adjuvanted capsomeres induce an antibody titre comparable to VLPs but superior to unadjuvanted capsomere formulations. Antibodies raised against GAS J8 peptide following immunization with chimeric J8-VP1 VLPs are bactericidal against a GAS reference strain. E. coli is easily and widely cultivated, and well understood, and delivers unparalleled volumetric productivity in industrial bioreactors. Indeed, recent results demonstrate that MuPyV VP1 can be produced in bioreactors at multi-gram-per-litre levels. The platform technology described here therefore has the potential to deliver safe and efficacious vaccine, quickly and cost effectively, at distributed manufacturing sites including those in less developed countries. Additionally, the unique advantages of VLPs including their stability on freeze drying, and the potential for intradermal and intranasal administration, suggest this technology may be suited to numerous diseases where adequate response requires large-scale and low-cost vaccine manufacture, in a way that is rapidly adaptable to temporal or geographical variation in pathogen molecular composition.
authors.affiliation: The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St. Lucia, QLD 4072, Australia. a.middelberg@uq.edu.au
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
authors.forename: Tania
authors.initials: T
authors.lastname: Rivera-Hernandez
authors.forename: Nani
authors.initials: N
authors.lastname: Wibowo
authors.forename: Linda H L
authors.initials: LH
authors.lastname: Lua
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Fan
authors.forename: Graham
authors.initials: G
authors.lastname: Magor
authors.forename: Cindy
authors.initials: C
authors.lastname: Chang
authors.forename: Yap P
authors.initials: YP
authors.lastname: Chuan
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001709:Biotechnology / Q000379:methods*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering / Q000379:methods; D051379:Mice; D011120:Polyomavirus / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods*; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022701:Virosomes / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D036022:Capsid Proteins; D011994:Recombinant Proteins; D022721:Vaccines, Virosome; D014763:Viral Matrix Proteins; D022701:Virosomes; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins