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

• Main Authors: Norpi, Abdin Shakirin Mohamad, Nordin, Muhammad Luqman, Ahmad, Nuraziemah, Katas, Haliza, Ahmad Fuaad, Abdullah Al-Hadi, Sukri, Asif, Marasini, Nirmal, Azmi, Fazren
• Format: Article
• Published: SHENYANG PHARMACEUTICAL UNIV 2022
• Subjects: RM Therapeutics. Pharmacology
• Online Access: http://eprints.um.edu.my/41998/

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). (C) 2022 Shenyang Pharmaceutical University. Published by Elsevier B.V.