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BIOGRAPHY:
Dr. Basombrío received his doctorate in medicine from the
Universidad Nacional de Buenos Aires in Argentina in 1980. In 1981 he
created and organized the Laboratory for Experimental Pathology at the
Department of Health Sciences of the National University of Salta, and
in 1992 he became principal investigator in CONICET. The laboratory has
since been upgraded to the status of a CONICET institute, of which he
is now director. Dr. Basombrío has received several honors and
prizes including the 1977 Pablo San Martin Prize and Gold Medal of the
Leukemia Foundation (FUNDALEU), induction as one of the "10 Jovenes
Sobresalientes" by the Junior Chamber of Buenos Aires (1980), election
to the National Academy of Medicine of Argentina as a corresponding
member (1995), the Bernardo Houssay Prize bestowed by CONICET (1988),
the Lepetit (1988), Qualitas (1995), and Redoxon (2000) prizes for
scientific achievement in experimental parasitology, and the Man of the
Year Prize, bestowed by TV Channel 11 of Salta. He is working on an
analysis of virulence genes in trypanosomatids causing Chagas' disease
and leishmaniasis, using gene-targeted mutations to create
non-pathogenic progenies for potential use as vaccines.
RESEARCH ABSTRACT SUMMARY:
Immunogenicity of Trypanosoma cruzi Mutants: Characterization of Biochemical Markers and Models of Protection Against Disease
Trypanosoma cruzi establishes lifelong infection. Partial
immunization can be achieved by experimental vaccines, often consisting
of parasite antigens plus adjuvants. However, this protection is not
long lasting and has not convincingly prevented tissue lesions or
alterations in heart function. Working with animal models, we were able
to establish in recent years that vaccination can indeed induce solid
and long-lasting resistance against infection and disease. But the
ability of a vaccine to do so seems to depend on two attributes that
raise safety issues: that live parasites be present in the immunogen
and that they retain, at least temporarily, some degree of infectivity.
Much of this evidence was obtained using the long-term,
culture-attenuated TCC strain. Recently, we started using two
gene-targeted mutants of T. cruzi, derived by homologous
recombination, as tools. A gp72-null strain retains the ability
to grow in vitro, in spite of a 1745-bp deletion of coding sequence
from both alleles of the gene. After eight years of laboratory
propagation in the absence of antibiotics, the stability of the
mutation was studied. Specific primer annealing sites and length of the
construct replacing the gene were analyzed. The deleted gene was still
absent; it was replaced by an antibiotic-resistance construct. In mice,
the mutated parasites were unable to sustain infection, but the animals
were protected against virulent T. cruzi. However, after one
year, the protection by gp72-null was no longer detectable, in
contrast with the persistently protective TCC strain. A second T.
cruzi mutant was analyzed, in which one allele of the cub
gene was deleted after homologous recombination with a
neomycin-resistance construct. This mutant displayed a remarkable,
though incomplete, reduction in virulence and the ability to protect
against virulent challenge. The possibility of knocking out one or more
genes from the TCC strain while retaining its capacity to provide
long-term protection is being explored in our laboratory.
Photo: Dominic Chaplin, Pine Creek Pictures
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