title: Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.
abstract: Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, Centre for Biomolecular Engineering, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Yap P
authors.initials: YP
authors.lastname: Chuan
authors.forename: Tania
authors.initials: T
authors.lastname: Rivera-Hernandez
authors.forename: Nani
authors.initials: N
authors.lastname: Wibowo
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Connors
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Fiona K
authors.initials: FK
authors.lastname: Hughes
authors.forename: Linda H L
authors.initials: LH
authors.lastname: Lua
authors.forename: Anton P J
authors.initials: AP
authors.lastname: Middelberg
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology*; D011120:Polyomavirus / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: D000941:Antigens; D004337:Drug Carriers; D007074:Immunoglobulin G; D010455:Peptides; D058425:Vaccines, Virus-Like Particle
keywords: biomolecular engineering; modular; pre-existing immunity; vaccine; virus-like particle