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Multi-Antigen Vaccination With Lpd Nanoparticles Containing Rgp63 and Rlmac1n Proteins Induced Effective Immune Response Against Leishmaniasis in Animal Model Publisher



Zamani P1 ; Alavizadeh SH1, 2 ; Fakhraee F1 ; Badiee A1, 2 ; Jalali SA3 ; Chavoshian O1 ; Khamesipour A4 ; Kheiri MT5 ; Mahboudi F5 ; Jaafari MR1, 2, 6
Authors
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Authors Affiliations
  1. 1. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  2. 2. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  3. 3. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
  6. 6. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Journal of Drug Delivery Science and Technology Published:2021


Abstract

An effective Leishmania vaccine must induce strong Th1 immune responses and generate long-term effectiveness in the host. To date, most designated anti-Leishmania vaccines have shown poor efficacy in clinical studies. One of the most effective approaches in enhancing the efficacy of vaccines to generate protective immunity is the use of multiple distinct antigens in a single vaccination regimen. For this reason, we investigated the immunogenicity and protective efficacy of liposomal formulation composed of DOTAP:Cholesterol, protamine and CpG ODNs (LPD NPs) containing rLmaC1N and rgp63 recombinant proteins (LPD-rLmaC1N/rgp63) as an effective vaccine. Then, we have investigated the immunogenicity and protective efficacy of LPD-rLmaC1N/rgp63 in experimental animal model of cutaneous leishmaniasis compared to free antigens. Our study showed that mice immunization with LPD-rLmaC1N/rgp63 significantly activates Th1 immune response and enhances IFN-γ production and IgG2a levels. Notably, LPD-rLmaC1N/rgp63 immunization greatly reduced the number of live parasites in the spleen and footpads of immunized mice compared to other vaccinated groups. As well, the thickness of footpad was remarkably smaller in mice immunized with LPD-rLmaC1N/rgp63. In conclusion, our study indicated that LPD-rLmaC1N/rgp63 could be regarded as a promising multiple-antigen candidate vaccine compared to single antigen counterparts to generate protective immunity against leishmaniasis. The potential advantages of this formulation may warrant further investigation. © 2021 Elsevier B.V.
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