Microbially synthesized modular virus-like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants

Chuan, Yap P., Wibowo, Nani, Connors, Natalie K., Wu, Yang, Hughes, Fiona K., Batzloff, Michael R., Lua, Linda H. L. and Middelberg, Anton P. J. (2013) Microbially synthesized modular virus-like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants. Biotechnology and Bioengineering, Early View 6: 1-9. doi:10.1002/bit.25172

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Author Chuan, Yap P.
Wibowo, Nani
Connors, Natalie K.
Wu, Yang
Hughes, Fiona K.
Batzloff, Michael R.
Lua, Linda H. L.
Middelberg, Anton P. J.
Title Microbially synthesized modular virus-like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants
Journal name Biotechnology and Bioengineering   Check publisher's open access policy
ISSN 0006-3592
1097-0290
Publication date 2013-12-28
Year available 2013
Sub-type Article (original research)
DOI 10.1002/bit.25172
Volume Early View
Issue 6
Start page 1
End page 9
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
Formatted abstract
Effective and low-cost vaccines are essential to control severe group A streptococcus (GAS) infections prevalent in low-income nations and the Australian aboriginal communities. Highly diverse and endemic circulating GAS strains mandate broad-coverage and customized vaccines. This study describes an approach to deliver cross-reactive antigens from endemic GAS strains using modular virus-like particle (VLP) and capsomere systems. The antigens studied were three heterologous N-terminal peptides (GAS1, GAS2, and GAS3) from the GAS surface M-protein that are specific to endemic strains in Australia Northern Territory Aboriginal communities. In vivo data presented here demonstrated salient characteristics of the modular delivery systems in the context of GAS vaccine design. First, the antigenic peptides, when delivered by unadjuvanted modular VLPs or adjuvanted capsomeres, induced high titers of peptide-specific IgG antibodies (over 1 × 104). Second, delivery by capsomere was superior to VLP for one of the peptides investigated (GAS3), demonstrating that the delivery system relative effectiveness was antigen-dependant. Third, significant cross-reactivity of GAS2-induced IgG with GAS1 was observed using either VLP or capsomere, showing the possibility of broad-coverage vaccine design using these delivery systems and cross-reactive antigens. Fourth, a formulation containing three pre-mixed modular VLPs, each at a low dose of 5 μg (corresponding to <600 ng of each GAS peptide), induced significant titers of IgGs specific to each peptide, demonstrating that a multivalent, broad-coverage VLP vaccine formulation was possible. In summary, the modular VLPs and capsomeres reported here demonstrate, with promising preliminary data, innovative ways to design GAS vaccines using VLP and capsomere delivery systems amenable to microbial synthesis, potentially adoptable by developing countries.
Keyword Group A streptococcus
M-protein
Virus-like particle
Capsomere cross-reactive
Vaccine
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 28 DEC 2013

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 3 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 08 Jan 2014, 11:27:59 EST by Linda Lua on behalf of Aust Institute for Bioengineering & Nanotechnology