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Investigation of physical mixtures versus disulfide crosslinking self-adjuvanting peptide-based subunit vaccines against Group A Streptococcus

2025/12/17 by Jingyi Fan, Jingwen Wang, Lantian Lu +12 · 2 citations
Dentistry · Immunology and Microbiology · Medicine · #Antibody #Antigen #Epitope #Group A #Immunotherapy and Immune Responses #Lipopeptide #Oral microbiology and periodontitis research #Peptide #Protein subunit #Streptococcal Infections and Treatments #Streptococcus #Streptococcus pyogenes

paper · doi:10.1016/j.ijpharm.2025.126513

published in International Journal of Pharmaceutics 689, 126513 (Elsevier BV)

openalex created_date 2025/12/17 · openalex publication_date 2025/12/17 · openalex updated_date 2026/07/29

Abstract

) as self-adjuvanting domains. Constructs were developed by direct conjugation or simple physical mixing, and compared to disulfide-crosslinked formulations containing one, two, or three cysteine residues. Immunisation studies in mice revealed that single-disulfide crosslinked constructs elicited stronger humoral responses than those with multiple crosslinks. However, physical mixtures of P-J8 with either lipopeptide or polyleucine induced significantly higher IgG titres, outperforming all crosslinked counterparts. These formulations also promoted enhanced dendritic cell maturation, with increased expression of MHC II and CD40, suggesting superior antigen presentation and T-cell activation. Furthermore, sera from immunised mice demonstrated potent opsonisation and bactericidal activity against clinical GAS isolates. Our findings highlight the promise of physical mixture formulations as simple, effective, and self-adjuvanting peptide vaccine platforms for GAS prevention.

Citations