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TRANSMISSION BLOCKING VACCINE STUDIES IN LElISHMANIASIS: I . LIPOPHOSPHOGLYCAN IS A PROMISING TRANSMISSION BLOCKING VACCINE MOLECULE AGAINST CUTANEOUS LEISHMANIASIS
Abstract
Background: New strategies for control of leishmaniasis is needed as chemotherapy using
antimonial drugs is prolonged, expensive, associated with side effects and relapses. Vector
control has limitations and a vaccine which may be the best approach is not available.
Objectives: To assess the level of inhibition of promastigote development and gut morphology
in infected Phlebotomus dubotcqi sandflies fed on different groups of BALBlc mice immunised
with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared
from L. major culture-derived promastigotes.
Methods: BALBlc mice were immunised adequately with Leishmania major-derived antigens
namely, crude whole para5ite ( WPA), recombinant 63 kilodalton glycoprotein (rgp63), LPG and
a cocktail composed of rgp63 plus LPG antigens . Laboratory reared Phlebotomus duboscqi
sandflies, the natural vector for I, major were later allowed to feed on immunised animals,
interrupted and allowed to continue feeding on infected animals for an equal amount of tirne until
they became fully engorged. The sandflies were maintained on apples as a carbohydrate source
in an insectary maintained at a temperature of 2S°C and 80% relative humidity. Some of the
sandflies were dissected on days 2,4 and 6 after feeding and observed using the light :and the
transmission electron microscopy for any changes in their gut morphology. The remaining
sandflies werealldissectdon thesixthday post-feeding and examinedfor procyclics,necton~onads,
haptomonads and metacyclic promastigote forms of Leishmania.
Results: Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail ant1 LPGimmunised
mice showed the lowest infection rates compared to control sandflies fed on saline
immunised mice (p<0.05). A significant number of procyclic promastigotes, th~e first
developmental form of the parasite in culture as well as in the sandfly was observed in
sandflies which fed on LPG-immunised mice (pe0.05). The dominant parasite form in
sandflies which fed on rgp63 or LPG-immunised mice was the nectomonad form but very few
of the infective metacyclic forms (pe0.05). Control sandflies fed on saline immunised or
infected mice alone displayed a normal pattern of parasite development up to the metacyclic
stage. Studies showed that two possible mechanisms through which immune sera from
immunised mice may came inhibition of parasite development is by exflagellation of
nectomonad forms and degeneration of the sandfly midgut epithelium as revealed by light
and electron microscopy studies respectively.
Conclusions: This studj has shown that immune-mediated transmission blocking rnay be
applied to Leishmania infections. Based on observation of the procyclic promastigoles, the
dominance of the nectomonad forms, low infectivity rates in sandflies fed on LPG-immunised
mice, we concluded that LPG stands out to be a promising transmission blocking vaccine
candidate in leishmaniasis.
antimonial drugs is prolonged, expensive, associated with side effects and relapses. Vector
control has limitations and a vaccine which may be the best approach is not available.
Objectives: To assess the level of inhibition of promastigote development and gut morphology
in infected Phlebotomus dubotcqi sandflies fed on different groups of BALBlc mice immunised
with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared
from L. major culture-derived promastigotes.
Methods: BALBlc mice were immunised adequately with Leishmania major-derived antigens
namely, crude whole para5ite ( WPA), recombinant 63 kilodalton glycoprotein (rgp63), LPG and
a cocktail composed of rgp63 plus LPG antigens . Laboratory reared Phlebotomus duboscqi
sandflies, the natural vector for I, major were later allowed to feed on immunised animals,
interrupted and allowed to continue feeding on infected animals for an equal amount of tirne until
they became fully engorged. The sandflies were maintained on apples as a carbohydrate source
in an insectary maintained at a temperature of 2S°C and 80% relative humidity. Some of the
sandflies were dissected on days 2,4 and 6 after feeding and observed using the light :and the
transmission electron microscopy for any changes in their gut morphology. The remaining
sandflies werealldissectdon thesixthday post-feeding and examinedfor procyclics,necton~onads,
haptomonads and metacyclic promastigote forms of Leishmania.
Results: Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail ant1 LPGimmunised
mice showed the lowest infection rates compared to control sandflies fed on saline
immunised mice (p<0.05). A significant number of procyclic promastigotes, th~e first
developmental form of the parasite in culture as well as in the sandfly was observed in
sandflies which fed on LPG-immunised mice (pe0.05). The dominant parasite form in
sandflies which fed on rgp63 or LPG-immunised mice was the nectomonad form but very few
of the infective metacyclic forms (pe0.05). Control sandflies fed on saline immunised or
infected mice alone displayed a normal pattern of parasite development up to the metacyclic
stage. Studies showed that two possible mechanisms through which immune sera from
immunised mice may came inhibition of parasite development is by exflagellation of
nectomonad forms and degeneration of the sandfly midgut epithelium as revealed by light
and electron microscopy studies respectively.
Conclusions: This studj has shown that immune-mediated transmission blocking rnay be
applied to Leishmania infections. Based on observation of the procyclic promastigoles, the
dominance of the nectomonad forms, low infectivity rates in sandflies fed on LPG-immunised
mice, we concluded that LPG stands out to be a promising transmission blocking vaccine
candidate in leishmaniasis.
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