New modular platform based on multi-adjuvanted amphiphilic chitosan nanoparticles for efficient lipopeptide vaccine delivery against group A streptococcus

• Published in: Asian journal of pharmceutical sciences 2022-05, Vol.17 (3), p.435-446
• Main Authors: Norpi, Abdin Shakirin Mohamad, Nordin, Muhammad Luqman, Ahmad, Nuraziemah, Katas, Haliza, Fuaad, Abdullah Al-Hadi Ahmad, Sukri, Asif, Marasini, Nirmal, Azmi, Fazren
• Format: Article
• Language: English
• Subjects: Amphiphilic chitosan nanoparticles; Group A streptococcus; Immunogenicity; Lipidation; Multi-adjuvanting delivery system; Original Research Paper; Peptide vaccine
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2022.04.002

An effective vaccine against group A streptococcus (GAS) is highly desirable for definitive control of GAS infections. In the present study, two variants of amphiphilic chitosan nanoparticles-based GAS vaccines were developed. The vaccines were primarily composed of encapsulated KLH protein (a source of T helper cell epitopes) and lipidated M-protein derived B cell peptide epitope (lipoJ14) within the amphiphilic structure of nanoparticles. The only difference between them was one of the nanoparticles vaccines received additional surface coating with poly (I:C). The formulated vaccines exhibited nanosized particles within the range of 220–240 nm. Cellular uptake study showed that nanoparticles vaccine without additional poly (I:C) coating has greater uptake by dendritic cells and macrophages compared to nanoparticles vaccine that was functionalized with poly (I:C). Both vaccines were found to be safe in mice and showed negligible cytotoxicity against HEK293 cells. Upon immunization in mice, both nanoparticle vaccines produced high antigen-specific antibodies titres that were regulated by a balanced Th1 and Th2 response compared to physical mixture. These antibodies elicited high opsonic activity against the tested GAS strains. Overall, our data demonstrated that amphiphilic chitosan nanoparticles platform induced a potent immune response even without additional inclusion of poly (I:C). [Display omitted] The formulated amphiphilic chitosan nanoparticles-based lipopeptide vaccine was capable in inducing a potent neutralizing antibody against group A streptococcus. The antibody productions were governed by a balanced Th1/Th2 polarization, which is necessary for optimal protective efficacy against group A streptococcus infections.