title: Structure-activity relationship for the development of a self-adjuvanting mucosally active lipopeptide vaccine against Streptococcus pyogenes.
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.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Mehfuz
authors.initials: M
authors.lastname: Zaman
authors.forename: Abu-Baker M
authors.initials: AB
authors.lastname: Abdel-Aal
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Zyta M
authors.initials: ZM
authors.lastname: Ziora
authors.forename: Michael R
authors.initials: MR
authors.lastname: Batzloff
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D013045:Species Specificity; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D013297:Streptococcus pyogenes / Q000737:chemistry* / Q000276:immunology; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007070:Immunoglobulin A; D055666:Lipopeptides; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein