Molecular Biology
and Vaccine Development in Plasmodium
The research activities in our laboratory
focus mainly in two areas of malaria: molecular biology
and vaccine development.
In the area of molecular biology, we
have constructed a genomic DNA library of P. vivax (the
most prevalent malarial parasite in Latin America and
responsible for 80 million annual cases worldwide), in
yeast artificial chromosomes (YACs) with parasite material
obtained from a single infected patient in the Brazilian
Amazon (1). Generating an unlimited source of parasite
material was of particular relevance since P. vivax cannot
be maintained continuously in in vitro culture. Significantly,
the availability of this reference library enabled us
to apply comparative genomics to address different aspects
of the pathology associated with P. vivax infections such
as antigenic variation (2), chloroquine resistance (3)
and identification of mapped microsatellite markers for
populational studies (unpublished). We are now following
up these studies given particular emphasis to the vir
genes of P. vivax to study their role in natural and experimental
infections. Thus, we are analyzing the expression of vir
genes in parasites obtained directly from human patients
as well as trying to determine their expression in single-infected
cells. Moreover, using transfection technologies we are
trying to express these genes in P. falciparum to determine
their role in virulence. Other molecular biology studies
in Plasmodium have been or are presently being pursued
in the laboratory, including one on the var multigene
family of P. falciparum in the Brazilian Amazon (see publications),
and attempts to establish an inducible system based on
a transcriptional transactivator in Plasmodium (unpublished)
In the area of vaccine development, we
have concentrated our efforts on the merozoite surface
protein 1 of P. vivax (PvMSP1) (4), and in particular
on the C-terminal region of the molecule, PvMSP119. We
have chosen PvMSP119 since studies on naturally acquired
immunity of vivax patients from the Brazilian Amazon have
revealed that this is the most immunogenic portion of
PvMSP1 and the only portion capable of eliciting a boost
effect upon new infections (5). Thus far, we have generated
an inmunogenic DNA recombinant plasmid of PvMSP119 (6),
and an inmunogenic transgenic Toxoplasma gondii expressing
PvMSP119 (unpublished).
Both constructs are now being tested in preclinical trials
and a transgenic P. falciparum expressing PvMSP119 to
address the importance of antibodies in the elicited responses
from monkeys, is being generated.
Image 1 |
Plasmodium vivax |
Image 2 |
VIR proteins of P. vivax |
Image 3 |
Recombinant Toxoplasma gondii
expressing PvMSP119 |
Research Interest Molecular Biology and
Vaccine Development in Malaria.
Research key words Malaria, Plasmodium,
molecular biology, virulent genes, vaccines.
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