The University of Queensland (UQ) filed patents on the use of MuPyV as a vaccine platform. L.H.L.L. and A.P.J.M. are named inventors on these patents and through their employment with UQ hold an indirect interest in this intellectual property. The other authors declare no conflict of interest.
Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine
Article first published online: 22 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 110, Issue 9, pages 2343–2351, September 2013
How to Cite
Chuan, Y. P., Rivera-Hernandez, T., Wibowo, N., Connors, N. K., Wu, Y., Hughes, F. K., Lua, L. H.L. and Middelberg, A. P.J. (2013), Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine. Biotechnol. Bioeng., 110: 2343–2351. doi: 10.1002/bit.24907
Yap P. Chuan and Tania Rivera-Hernandez contributed equally to this work.
- Issue published online: 23 JUL 2013
- Article first published online: 22 APR 2013
- Accepted manuscript online: 26 MAR 2013 09:20AM EST
- Manuscript Accepted: 12 MAR 2013
- Manuscript Revised: 8 MAR 2013
- Manuscript Received: 26 NOV 2012
- Queensland Government's “National and International Research Alliances” Program. Grant Number: NIRAP 2010000484
- Queensland Government. Grant Number: 2010 Premier Fellow
- virus-like particle;
- pre-existing immunity;
- biomolecular engineering;
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. Biotechnol. Bioeng. 2013; 110:2343–2351. © 2013 Wiley Periodicals, Inc.