Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates

Chan, Amy, Hussein, Waleed M., Ghaffar, Khairunnisa Abdul, Marasini, Nirmal, Mostafa, Ahmed, Eskandari, Sharareh, Batzloff, Michael R., Good, Michael F., Skwarczynski, Mariusz and Toth, Istvan (2016) Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates. Bioorganic and Medicinal Chemistry, 24 14: 3095-3101. doi:10.1016/j.bmc.2016.03.063


Author Chan, Amy
Hussein, Waleed M.
Ghaffar, Khairunnisa Abdul
Marasini, Nirmal
Mostafa, Ahmed
Eskandari, Sharareh
Batzloff, Michael R.
Good, Michael F.
Skwarczynski, Mariusz
Toth, Istvan
Title Structure-activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates
Journal name Bioorganic and Medicinal Chemistry   Check publisher's open access policy
ISSN 0968-0896
1464-3391
Publication date 2016
Sub-type Article (original research)
DOI 10.1016/j.bmc.2016.03.063
Volume 24
Issue 14
Start page 3095
End page 3101
Total pages 7
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2017
Language eng
Formatted abstract
Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure–activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure.
Keyword Adjuvant
Copper-catalysed azide–alkyne cycloaddition
Group A Streptococcus
Lipopeptides
Peptide vaccine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Fri, 03 Jun 2016, 10:31:23 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences