Structure-Activity Relationship for the Development of a Self-Adjuvanting Mucosally Active Lipopeptide Vaccine against Streptococcus pyogenes

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Zaman, Mehfuz
Abdel-Aal, Abu-Baker M
Fujita, Yoshio
Ziora, Zyta M
Batzloff, Michael R
Good, Michael F
Toth, Istvan
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2012
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Abstract

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.

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Journal of Medicinal Chemistry

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55

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19

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Medicinal and biomolecular chemistry

Organic chemistry

Bacteriology

Pharmacology and pharmaceutical sciences

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