Live attenuated Leishmania major p27 gene knockout as a novel vaccine candidate: A study on safety, protective immunity and efficacy against canine leishmaniasis caused by Leishmania infantum.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6254 (Electronic) Linking ISSN: 0001706X NLM ISO Abbreviation: Acta Trop Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Basel.
    • Subject Terms:
      Dog Diseases*/prevention & control ; Leishmania infantum*/genetics ; Leishmania major*/genetics ; Leishmaniasis* ; Leishmaniasis Vaccines* ; Leishmaniasis, Visceral*/prevention & control ; Leishmaniasis, Visceral*/veterinary; Animals ; Dogs ; Female ; Gene Knockout Techniques ; Mice ; Mice, Inbred BALB C
    • Abstract:
      Canine leishmaniasis (CanL) is an important parasitic e disease caused by Leishmania infantum and is transmitted by female phlebotomine sand flies primarily between canines and secondarily to humans. Recently, we showed that immunization with Leishmania major p27 gene knockout (Lmp27 -/- ) as a live attenuated vaccine was safe, induced immunogenicity, and protected against the development cutaneous and visceral leishmaniasis in mice. The p27 protein is a component of the COX protein complex which is responsible for ATP production. In this study, we analyzed the Lmp27 -/- candidate vaccine potential with this regard to the safety and induction of immunogenicity and protection against CanL. Variables such a clinical manifestation, anti-Leishmania antibodies using direct agglutination test (DAT), lymphocyte proliferation, delayed-type hypersensitivity (DTH), bone marrow aspiration (BMA) and parasite burden using parasitological and molecular examinations were measured. The results demonstrated that the Lmp27 -/- vaccinated group showed no clinical signs after inoculation with Lmp27 -/- mutant during a 12-month follow-up, and had significantly higher T-cell responses (Lymphocyte proliferation and DTH), lower seroconversion and parasite burdens following a challenge inoculation with L. infantum after 6-mounth. In conclusion, vaccination with Lmp27 -/- parasites would be safe and provide significant immunoprotectivity and efficacy against infection with wild type (WT) L. infantum.
      (Copyright © 2021 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Immunogenicity; Leishmania infantum; Leishmania major; Protection; dog; p27 gene knockout
    • Accession Number:
      0 (Leishmaniasis Vaccines)
    • Publication Date:
      Date Created: 20211011 Date Completed: 20211129 Latest Revision: 20211129
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.actatropica.2021.106153
    • Accession Number:
      34634264