| Autor: |
Zaman M; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia., Abdel-Aal AB, Fujita Y, Ziora ZM, Batzloff MR, Good MF, Toth I |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2012 Oct 11; Vol. 55 (19), pp. 8515-23. Date of Electronic Publication: 2012 Sep 25. |
| DOI: |
10.1021/jm301074n |
| Abstrakt: |
Infection with group A streptococcus (GAS) can result in a number of diseases, some of which are potentially life-threatening. The oral-nasal mucosa is a primary site of GAS infection, and a mucosally active vaccine candidate could form the basis of an antidisease and transmission-blocking GAS vaccine. In the present study, a peptide from the GAS M protein (J14) representing a B cell epitope was incorporated alongside a universal T cell helper epitope and a Toll-like receptor 2 targeting lipid moiety to form lipopeptide constructs. Through structure activity studies, we identified a vaccine candidate that induces J14-specific mucosal and systemic antibody responses when administered intranasally without additional adjuvants. The systemic antibodies elicited were capable of inhibiting the growth of GAS. In addition, J14-specific mucosal antibodies corresponded with reduced throat colonization after respiratory GAS challenge. These preclinical experiments show that this lipopeptide could form the basis of an optimal needle-free mucosal GAS vaccine. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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