title: Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119.
abstract: Transdermal immunization results in poor immunogenicity, which can be attributed to poor permeability of antigens through the skin. Therefore, elastic liposome, ultradeformable lipid vesicles, may overcome the challenges faced during transdermal immunization. This versatile carrier proves better vehicle for transcutaneous delivery of protein, peptide and nucleic acid antigens. The present results are suggestive of improved immunogenicity of carboxyl-terminal 19 kDa fragment of merozoite surface protein-1 (PfMSP-119) of Plasmodium falciparum when administered subcutaneously through elastic liposomes. The prepared elastic liposomes were characterized with respect to vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in vitro release. Humoral and cell-mediated immune (CMI) response elicited by topically applied PfMSP-119-loaded elastic liposomes, intramuscularly administered alum-adsorbed PfMSP-119 solution, and topically applied PfMSP-119-loaded conventional liposomes were compared and normalized with vehicle control. Results suggest greater transcutaneous immunization via elastic liposomes, and induced robust and perdurable IgG-specific antibody and cytophilic isotype responses. We report to have achieved sizeable CMI activating factor (IFNγ), a crucial player in conferring resistance to asexual blood stage malaria, responses with elastic liposomes when compared with other formulations. The fluorescence microscopy and histopathology results are suggestive of prominent skin permeation and biodistribution, and demonstrate efficient delivery of malaria antigen via elastic liposomes to immunocompetent Langerhans cells (LC) and lymphatics. In conclusion, elastic liposomal formulation provided greater entrapment efficiency, enhanced penetration and heightened and long-lasting immune response. Moreover, effective immunoadjuvant property of this carrier justifies its potential for improved vaccine delivery, and opens new avenues to explore further on the development of malaria vaccine.
authors.affiliation: Department of Periodontics, College of Dental Medicine, Georgia Regents University, Augusta, GA, USA; Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, MP, India. Electronic address: rajeev.dbt@gmail.com.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Tyagi
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Neeraj K
authors.initials: NK
authors.lastname: Garg
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, MP, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Jadon
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Tejram
authors.initials: T
authors.lastname: Sahu
authors.affiliation: Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Katare
authors.affiliation: Institute of Science, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad 382 481, Gujarat, India.
authors.forename: Sarat K
authors.initials: SK
authors.lastname: Dalai
authors.affiliation: Translational Health Science and Technology Institute (an autonomous institute of Department of Biotechnology, Govt. of India), NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121 001, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine (inStem), National Centre for Biological Sciences (NCBS), Bangalore 560065, India.
authors.forename: Srujan K
authors.initials: SK
authors.lastname: Marepally
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology* / Q000493:pharmacokinetics; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D008081:Liposomes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D022223:Vaccines, Subunit
keywords: Cellular and humoral immunity; Elastic liposome; Immunization; Langerhans cells; MSP-119; Transdermal delivery; Vaccine