Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus

Olive, Colleen, Ho, Mei‐Fong, Dyer, Joanne, Lincoln, Douglas, Barozzi, Nadia, Toth, Istvan and Good, Michael F. (2006) Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus. Journal of Infectious Diseases, 193 12: 1666-1676. doi:10.1086/504266


Author Olive, Colleen
Ho, Mei‐Fong
Dyer, Joanne
Lincoln, Douglas
Barozzi, Nadia
Toth, Istvan
Good, Michael F.
Title Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
Publication date 2006-06-15
Sub-type Article (original research)
DOI 10.1086/504266
Open Access Status Not yet assessed
Volume 193
Issue 12
Start page 1666
End page 1676
Total pages 11
Place of publication Chicago
Publisher University of Chicago Press
Language eng
Subject C1
250302 Biological and Medical Chemistry
730101 Infectious diseases
Abstract Background. The development of a vaccine to prevent infection with group A streptococcus (GAS) is hampered by the widespread diversity of circulating GAS strains and M protein types, and it is widely believed that a multivalent vaccine would provide better protective immunity. Methods. We investigated the efficacy of incorporating 3 M protein serotypic amino-terminal epitopes from GAS isolates that are common in Australian Aboriginal communities and a conformational epitope from the conserved carboxy-terminal C-repeat region into a single synthetic lipid core peptide (LCP) vaccine construct in inducing broadly protective immune responses against GAS after parenteral delivery to mice. Results. Immunization with the tetraepitopic LCP vaccine construct led to high titers of systemic, antigen-specific IgG responses and the induction of broadly protective immune responses, as was demonstrated by the ability of immune serum to opsonize multiple GAS strains. Systemic challenge of mice with a lethal dose of GAS given 60 or 300 days after primary immunization showed that, compared with the control mice, the vaccinated mice were significantly protected against GAS infection, demonstrating that the vaccination stimulated long-lasting protective immunity. Conclusions. These data support the efficacy of the LCP vaccine delivery system in the development of a synthetic, multiepitopic vaccine for the prevention of GAS infection.
Formatted abstract
Background.
The development of a vaccine to prevent infection with group A streptococcus (GAS) is hampered by the widespread diversity of circulating GAS strains and M protein types, and it is widely believed that a multivalent vaccine would provide better protective immunity.

Methods.
We investigated the efficacy of incorporating 3 M protein serotypic amino‐terminal epitopes from GAS isolates that are common in Australian Aboriginal communities and a conformational epitope from the conserved carboxy‐terminal C‐repeat region into a single synthetic lipid core peptide (LCP) vaccine construct in inducing broadly protective immune responses against GAS after parenteral delivery to mice.

Results.
Immunization with the tetraepitopic LCP vaccine construct led to high titers of systemic, antigen‐specific IgG responses and the induction of broadly protective immune responses, as was demonstrated by the ability of immune serum to opsonize multiple GAS strains. Systemic challenge of mice with a lethal dose of GAS given 60 or 300 days after primary immunization showed that, compared with the control mice, the vaccinated mice were significantly protected against GAS infection, demonstrating that the vaccination stimulated long‐lasting protective immunity.

Conclusions.
These data support the efficacy of the LCP vaccine delivery system in the development of a synthetic, multiepitopic vaccine for the prevention of GAS infection.

Keyword Infectious Diseases
M-protein
T-cell
Intranasal Immunization
Synthetic Peptide
Conserved Region
B-cell
Mucosal Colonization
Epitopes
Antibodies
Mice
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Pharmacy Publications
 
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Created: Wed, 15 Aug 2007, 18:58:59 EST