Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine

Chuan, Yap P., Rivera-Hernandez, Tania, Wibowo, Nani, Connors, Natalie K., Wu, Yang, Hughes, Fiona K., Lua, Linda H. L. and Middelberg, Anton P. J. (2013) Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine. Biotechnology and Bioengineering, 110 9: 2343-2351. doi:10.1002/bit.24907


Author Chuan, Yap P.
Rivera-Hernandez, Tania
Wibowo, Nani
Connors, Natalie K.
Wu, Yang
Hughes, Fiona K.
Lua, Linda H. L.
Middelberg, Anton P. J.
Title Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine
Journal name Biotechnology and Bioengineering   Check publisher's open access policy
ISSN 0006-3592
1097-0290
Publication date 2013-09
Sub-type Article (original research)
DOI 10.1002/bit.24907
Volume 110
Issue 9
Start page 2343
End page 2351
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
Formatted 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.
Keyword Virus-like particle
Pre-existing immunity
Vaccine
Biomolecular engineering
Modular
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 18 Sep 2013, 13:58:25 EST by Cathy Fouhy on behalf of Aust Institute for Bioengineering & Nanotechnology