Polyacrylate–Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus

Abstract

Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.

Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein

“…To test the opsonic activity of the vaccines anti-J8 and anti-88/30 antibodies in vitro, we used seven randomly selected GAS isolates which was an innovation to the previous studies i.e., five strains or less [ 32 , 33 , 49 , 50 ]. The opsonization performed in this study was on seven clinical isolates of GAS isolated from a local Queensland hospital.…”

Chemical Conjugation Strategies for the Development of Protein-Based Subunit Nanovaccines

“…However, the use of copper wire as a sole reagent has also been reported [66][67][68][69]. CuAAC is a well-established method that has been extensively used for peptide-peptide or peptide-polymer conjugation [70,71]. The technique can be performed in living cells to modify cellular proteins, but yield from in vivo conjugation is low [72].…”

Cell-Penetrating Peptides-Based Liposomal Delivery System Enhanced Immunogenicity of Peptide-Based Vaccine against Group A Streptococcus

“…Opsonization assays were performed as previously reported [ 36 , 37 ]. Bacteria were streaked onto Todd Hewitt Broth (THB) agar plates supplemented with 5% yeast extract and incubated at 37 °C for 24 h. A single bacterial colony was transferred to THB (5 mL) supplemented with 5% yeast extract and incubated for another 24 h at 37 °C to obtain ~10 7 colony forming units (CFU)/mL.…”