Transdermal Immunization of Elastic Liposome-Laden Recombinant Chimeric Fusion Protein of P. falciparum (PfMSP-Fu24) Mounts Protective Immune Response

Abstract

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (<i>Pf</i>MSP-Fu₂₄) of <i>Plasmodium falciparum</i> exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of <i>Pf</i>MSP-Fu₂₄ conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the <i>Pf</i>MSP-Fu₂₄ upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered <i>Pf</i>MSP-Fu₂₄-laden elastic liposomes (EL-<i>Pf</i>MSP-Fu₂₄) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-<i>Pf</i>MSP-Fu₂₄ and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-<i>Pf</i>MSP-Fu₂₄ through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-<i>Pf</i>MSP-Fu₂₄ was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against <i>Pf</i>MSP-Fu₂₄ and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.