4.5 Article

Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P-falciparum surface antigen, MSP-119

Journal

VACCINE
Volume 33, Issue 36, Pages 4630-4638

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.06.054

Keywords

Elastic liposome; Transdermal delivery; MSP-119; Langerhans cells; Cellular and humoral immunity; Vaccine; Immunization

Funding

  1. Department of Biotechnology (DBT), New Delhi, India
  2. Council of Scientific and Industrial Research (CSIR HRDG) New Delhi, India

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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-1(19)) 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-1(19)-loaded elastic liposomes, intramuscularly administered alum-adsorbed PfMSP-1(19) solution, and topically applied PfMSP-1(19)-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 (IFN gamma), 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. (C) 2015 Elsevier Ltd. All rights reserved.

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