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Vaccine development against cutaneous leishmaniasis. Subcutaneous administration of radioattenuated parasites protects CBA mice against virulent Leishmania major challenge
Author(s) -
RIVIER D.,
SHAH R.,
BOVAY P.,
MAUEL J.
Publication year - 1993
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/j.1365-3024.1993.tb00587.x
Subject(s) - amastigote , virulence , biology , leishmania major , leishmania , microbiology and biotechnology , cutaneous leishmaniasis , leishmaniasis , heterologous , kinetoplastida , subcutaneous injection , virology , inoculation , immunology , parasite hosting , malaria , biochemistry , protozoal disease , bioinformatics , world wide web , computer science , gene
Summary Experiments described in this paper were aimed at determining whether subcutaneous inoculation of live, avirulent Leishmania major would protect mice against infection by the virulent parasite. To this effect, promastigotes or amastigotes of a highly virulent strain of L. major (MRHO/IR/76), used in human trials of leishmanization, and which induces non‐healing skin lesions in both CBA and BALB/c mice, were rendered non‐pathogenic by gamma irradiation. A dose of 150 krad was required to abrogate the virulence of the parasite as tested on BALB/c mice. Strikingly, however, not all leishmanias were completely inactivated by this procedure since live parasites were detected in the footpads and/or the inguinal lymph nodes as long as 28 days (CBA) or 18 weeks (BALB/c) after injection. Furthermore, 150 krad‐irradiated promastigotes retained the capacity to transform into amastigotes intracellularly in vitro. Subcutaneous inoculation of this irradiated ‘vaccine’ confered onto CBA mice a high degree of protection against challenge by both the homologous and a heterologous (MRHO/SU/59/P) strains of L. major. Lymph node cells from protected animals acquired the capacity to activate infected macrophages in vitro to kill intracellular L. major. To allow for maximum development of immunoprotection, the irradiated promastigotes had to remain viable, perhaps reflecting a requirement for transformation into amastigotes in the vaccinated host.