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

作　　者：Abdin Shakirin Mohamad Norpi Muhammad Luqman Nordin Nuraziemah Ahmad Haliza Katas Abdullah Al-Hadi Ahmad Fuaad Asif Sukri Nirmal Marasini Fazren Azmi 

机构地区：[1]Centre for Drug Delivery Technology,Faculty of Pharmacy,Universiti Kebangsaan Malaysia,Kuala Lumpur 50300,Malaysia [2]Faculty Pharmacy and Health Sciences,Universiti Kuala Lumpur,Royal College of Medicine Perak,Perak 30450,Malaysia [3]Faculty of Veterinary Medicine,Universiti Malaysia Kelantan,Kelantan 16100,Malaysia [4]Department of Chemistry,Faculty of Science,Universiti Malaya,Kuala Lumpur 50603,Malaysia [5]Universiti Teknologi Mara(UiTM),Bandar Puncak Alam,Integrative Pharmacogenomics Institute(iPROMISE),Selangor 43200,Malaysia [6]School of Biomedical Sciences,The University of Queensland,St.Lucia QLD 4072,Australia

出　　处：《Asian Journal of Pharmaceutical Sciences》2022年第3期435-446,共12页亚洲药物制剂科学（英文）

基　　金：supported financially by Universiti Kebangsaan Malaysia(UKM),Malaysia[DCP-2017-003/2].

摘　　要：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 themwas 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).

关 键 词：Amphiphilic chitosan nanoparticles Peptide vaccine LIPIDATION Multi-adjuvanting delivery system IMMUNOGENICITY Group A streptococcus 

分 类 号：R392-33[医药卫生—免疫学]