Title: Molecular aspects of sand fly-based vaccine development
Abstract: The emergence and reemergence of vector-borne diseases
pose significant threats to humans and other animals worldwide.
Although vector control relies mostly on insecticides, the
emergence of insecticide resistance urges for the development of
new strategies to control the spread of such diseases. For sand
fly-transmitted leishmaniasis, Transmission Blocking Vaccines (TBV)
may constitute a feasible strategy to impair Leishmania
transmission from infected to uninfected vertebrate hosts.
Moreover, sand fly saliva-based vaccines represent an alternative
or complementary approach as these vaccines protect different
mammalian hosts against Leishmania. Based on the potential use of
sand fly molecules as vaccines against leishmaniasis, we assessed
the potential of Phlebotomus papatasi midgut secreted proteins as
TBV candidates and the expression variability of sand fly salivary
gland genes. Regarding the TBV approach, we took advantage of the
RNA interference (RNAi) technique to evaluate the effects of
knocking down P. papatasi midgut-specific genes on Leishmania major
development within the sand fly midgut. Whereas peritrophin 1
(PpPer1) knock down led to increased Le. major load by 39%,
knocking down chitinase 1 (PpChit1) reduced Le. major load in P.
papatasi midguts by 63%. Thus, our data strongly suggest that
PpChit1 constitutes a potential target for TBV approaches against
Leishmania transmission in endemic areas. Concerning protective
vaccines based on salivary gland secreted proteins, we searched for
expression polymorphism in selected salivary gland genes in natural
and colonized populations of P. papatasi. Significant differences
in salivary gland gene expression were not only exhibited in P.
papatasi specimens collected in different geographic habitats but
also seasonal difference in gene expression was displayed by
specimens belonging to the same population. As antigen dose is an
important component of immune responses, different doses of
salivary protein inoculated into host skin may interfere with
vaccine protection. Thus, the efficacy of sand fly saliva-based
vaccine upon exposure to different salivary protein doses must be
evaluated before deployment in endemic areas. Our data also ruled
out some biotic factors as responsible for fine-tuning the
expression of such genes. Overall, this dissertation makes
significant contribution to the development of sand fly-based
vaccines against leishmaniasis.
Publication Year: 2011
Publication Date: 2011-01-01
Language: en
Type: dissertation
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