Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: Structure-activity relationship

Zaman, Mehfuz, Abdel-Aal, Abu-Baker M., Fujita, Yoshio, Phillipps, Karen S. M., Batzloff, Michael R., Good, Michael F. and Toth, Istvan (2012) Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: Structure-activity relationship. PLoS One, 7 1: e30146.1-e30146.7. doi:10.1371/journal.pone.0030146


Author Zaman, Mehfuz
Abdel-Aal, Abu-Baker M.
Fujita, Yoshio
Phillipps, Karen S. M.
Batzloff, Michael R.
Good, Michael F.
Toth, Istvan
Title Immunological evaluation of lipopeptide group A streptococcus (GAS) vaccine: Structure-activity relationship
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2012-01-12
Sub-type Article (original research)
DOI 10.1371/journal.pone.0030146
Open Access Status DOI
Volume 7
Issue 1
Start page e30146.1
End page e30146.7
Total pages 7
Editor Vladimir Brusic
Place of publication San Francisco, CA, U.S.A.
Publisher Public Library of Science
Collection year 2013
Language eng
Formatted abstract
Streptococcus pyogenes (group A streptococcus, GAS) is a Gram-positive bacterial pathogen responsible for a wide variety of diseases. To date, GAS vaccine development has focused primarily on the M-protein. The M-protein is highly variable at the amino (N)-terminus (determining serotype) but is conserved at the carboxyl (C)-terminus. Previously a 29 amino acid peptide (named J14) from the conserved region of the M-protein was identified as a potential vaccine candidate. J14 was capable of eliciting protective antibodies that recognized many GAS serotypes when co-administered with immuno-stimulants. This minimal epitope however showed no immunogenicity when administered alone. In an attempt overcome this immunological non-responsiveness, we developed a self-adjuvanting vaccine candidate composed of three components: the B-cell epitope (J14), a universal helper T-cell epitope (P25) and a lipid moiety consisting of lipoamino acids (Laas) which target Toll-like receptor 2 (TLR2). Immunological evaluation in B10.BR (H-2k) mice demonstrated that the epitope attachment to the point of lipid moiety, and the length of the Laa alkyl chain have a profound effect on vaccine immunogenicity after intranasal administration. It was demonstrated that a vaccine featuring C-terminal lipid moiety containing alkyl chains of 16 carbons, with P25 located at the N-terminus, and J14 attached to the side chain of a central lysine residue was capable of inducing optimal antibody response. These findings have considerable relevance to the development of a broad spectrum J14-based GAS vaccine and in particular provided a rational basis for peptide vaccine design based on this self-adjuvanting lipopeptide technology.

Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published 12 January 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 20 Jan 2012, 08:28:44 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences