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 (PfMSP-Fu₂₄) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu₂₄ conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu₂₄ upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu₂₄-laden elastic liposomes (EL-PfMSP-Fu₂₄) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-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-PfMSP-Fu₂₄ through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-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 PfMSP-Fu₂₄ and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.

Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete sterile protection against Plasmodia liver-stage (LS) infection that lasts about six to nine months in mice. We have found that the intermittent infectious sporozoite challenge to immune mice following RAS vaccination extends the longevity of sterile protection by maintaining CD8+T cell memory responses to LS infection. It is reported that CD8α+DCs are involved in the induction of LS specific CD8+T cells following RAS or genetically attenuated parasite (GAP) vaccination. In this study, we demonstrate that CD8α+DCs respond differently to infectious sporozoite or RAS inoculation. The higher accumulation and activation of CD8α+DCs was seen in the liver in response to infectious sporozoite 72 hr post inoculation, and found to be associated with higher expression of chemokines (CCL-20 and CCL-21) and Type-I interferon response via Toll-like receptor (TLR) (Toll-like receptor) signalling in liver. Moreover, the infectious sporozoites was found to induce qualitative changes in terms of the increased MHCII expression as well as co-stimulatory molecules including CD40 on the CD8α+DCs compared to RAS inoculation. We have also found that infectious sporozoite challenge increased CD40L expressing CD4+T cells, which could help CD8+T cells in the liver through ‘licensing’ of the APCs. Our results suggest that infectious sporozoite challenge to prior RAS immunized mice modulates the CD8α+DCs, which might be shaping the fate of memory CD8+T cells against Plasmodium LS infection.

Poly(I:C) and R848, synthetic ligands that activate Toll-like receptor 3 (TLR3) and TLR7/8 respectively, have been well-established for their ability to stimulate the immune system and induce antigen-specific immune responses. These ligands are capable of inducing the production of cytokines and chemokines, and hence support the activation and differentiation of B and T cells. We saw the long-lasting and perdurable immune responses by these adjuvants essentially required for an efficacious subunit vaccine. In this study, we investigated the potential of poly(I:C) and R848 to elicit B and T cell responses to the OVA antigen. We assessed the stimulatory effects of these ligands on the immune system, their impact on B and T cell activation, and their ability to enhanced generation of B and T cells. Collectively, our findings contribute to the understanding how poly(I:C) and R848 can be utilized as an adjuvant system to enhance immune responses to protein-based subunit vaccines. In the end, this work provides insights for the development of novel vaccination strategies and improving the vaccine efficacy. Present work shall help formulate newer strategies for subunit vaccines to address the infectious diseases.