Development of a new live attenuated Leishmania major p27 gene knockout: Safety and immunogenicity evaluation in BALB/c mice
| Autor: | Sassan Rezaei, Mohammad Reza Eshraghian, Hamid Eslami, Samira Elikaee, Hossein Keshavarz, Mehdi Mohebali, Ali Khamesipour |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Immunology Mutant Antibodies Protozoan Leishmaniasis Cutaneous Spleen Antigens Protozoan Biology Vaccines Attenuated Microbiology BALB/c 03 medical and health sciences Gene Knockout Techniques Mice 0302 clinical medicine Proliferating Cell Nuclear Antigen Splenocyte medicine Animals Leishmania major Leishmaniasis Vaccines Gene knockout Cell Proliferation Skin Infectivity Mice Inbred BALB C Immunogenicity Macrophages biology.organism_classification 030104 developmental biology medicine.anatomical_structure Liver Antibody Formation 030215 immunology |
| Zdroj: | Cellular immunology. 332 |
| ISSN: | 1090-2163 |
| Popis: | Genetically modifying Leishmania major by eliminating essential virulence genes have been proposed as potential vaccine candidates. p27 is a COX component that is responsible for ATP synthesis. In this study a new mutant of Leishmania major (L. major) (MRHO/IR/75/ER) lacking the p27 gene (Lmp27-/-) was produced via homologous recombination, marking the first time such a strain has been developed. In vitro macrophage infectivity and In vivo safety, and overall immunogenicity were evaluated at various time periods following inoculation into BALB/c mice. Skin lesion development, parasite burden in the liver and spleen, cytokine and antibody levels, splenocyte proliferation, and delayed type hypersensitivity (DTH) were the measured variables. Results demonstrated that the Lmp27-/- mutant caused no skin lesion, had low parasitic burdens in the liver and spleen, and had a significantly increased Th1 response. These results suggest that the Lmp27-/- mutant has the potential to be evaluated as a vaccine candidate. |
| Databáze: | OpenAIRE |
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