Transmission blocking vaccine studies in leishmaniasis : I. Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis

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. To assess the level of inhibition of promasti...

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Veröffentlicht in:East African medical journal 2001-02, Vol.78 (2), p.84-89
Hauptverfasser: TONUI, W. K, MBATI, P. A, ANJILI, C. O, ORAGO, A. S, TURCO, S. J, GITHURE, J. I, KOECH, D. K
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container_title East African medical journal
container_volume 78
creator TONUI, W. K
MBATI, P. A
ANJILI, C. O
ORAGO, A. S
TURCO, S. J
GITHURE, J. I
KOECH, D. K
description 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. To assess the level of inhibition of promastigote development and gut morphology in infected Phlebotomus duboscqi sandflies fed on different groups of BALB/c mice immunised with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared from L. major culture-derived promastigotes. BALB/c mice were immunised adequately with Leishmania major-derived antigens namely, crude whole parasite (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 L. major were later allowed to feed on immunised animals, interrupted and allowed to continue feeding on infected animals for an equal amount of time until they became fully engorged. The sandflies were maintained on apples as a carbohydrate source in an insectary maintained at a temperature of 25 degrees 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 were all dissected on the sixth day post-feeding and examined for procyclics, nectomonads, haptomonads and metacyclic promastigote forms of Leishmania. Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail and LPG-immunised mice showed the lowest infection rates compared to control sandflies fed on saline immunised mice (p < 0.05). A significant number of procyclic promastigotes, the first developmental form of the parasite in culture as well as in the sandfly was observed in sandflies which fed on LPG-immunised mice (p < 0.05). 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 (p < 0.05). 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 cause inhibition of parasite development is by exflagellation of nectomonad forms and degeneration of the sandfly midgut epithelium as revealed by light and e
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Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>TONUI, W. K ; MBATI, P. A ; ANJILI, C. O ; ORAGO, A. S ; TURCO, S. J ; GITHURE, J. I ; KOECH, D. K</creator><creatorcontrib>TONUI, W. K ; MBATI, P. A ; ANJILI, C. O ; ORAGO, A. S ; TURCO, S. J ; GITHURE, J. I ; KOECH, D. K</creatorcontrib><description>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. 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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 were all dissected on the sixth day post-feeding and examined for procyclics, nectomonads, haptomonads and metacyclic promastigote forms of Leishmania. Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail and LPG-immunised mice showed the lowest infection rates compared to control sandflies fed on saline immunised mice (p &lt; 0.05). A significant number of procyclic promastigotes, the first developmental form of the parasite in culture as well as in the sandfly was observed in sandflies which fed on LPG-immunised mice (p &lt; 0.05). 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 (p &lt; 0.05). 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K</creatorcontrib><creatorcontrib>MBATI, P. A</creatorcontrib><creatorcontrib>ANJILI, C. O</creatorcontrib><creatorcontrib>ORAGO, A. S</creatorcontrib><creatorcontrib>TURCO, S. J</creatorcontrib><creatorcontrib>GITHURE, J. I</creatorcontrib><creatorcontrib>KOECH, D. K</creatorcontrib><title>Transmission blocking vaccine studies in leishmaniasis : I. Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis</title><title>East African medical journal</title><addtitle>East Afr Med J</addtitle><description>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. To assess the level of inhibition of promastigote development and gut morphology in infected Phlebotomus duboscqi sandflies fed on different groups of BALB/c mice immunised with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared from L. major culture-derived promastigotes. BALB/c mice were immunised adequately with Leishmania major-derived antigens namely, crude whole parasite (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 L. major were later allowed to feed on immunised animals, interrupted and allowed to continue feeding on infected animals for an equal amount of time until they became fully engorged. The sandflies were maintained on apples as a carbohydrate source in an insectary maintained at a temperature of 25 degrees C and 80% relative humidity. 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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 cause 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. This study has shown that immune-mediated transmission blocking may be applied to Leishmania infections. Based on observation of the procyclic promastigotes, 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.</description><subject>Animals</subject><subject>Antibodies, Protozoan - blood</subject><subject>Biological and medical sciences</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Epidemiology. Vaccinations</subject><subject>General aspects</subject><subject>Glycosphingolipids - immunology</subject><subject>Infectious diseases</subject><subject>Insect Vectors - parasitology</subject><subject>Leishmania major - immunology</subject><subject>Leishmaniasis, Cutaneous - blood</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Leishmaniasis, Cutaneous - prevention &amp; control</subject><subject>Leishmaniasis, Cutaneous - transmission</subject><subject>Medical sciences</subject><subject>Metalloendopeptidases - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Phlebotomus - parasitology</subject><subject>Protozoan Vaccines - immunology</subject><subject>Tropical medicine</subject><issn>0012-835X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD9PwzAQxT2AaCnMbMgDYkuwnaR12BDiT6VKLEViiy7upXVxnNBLKvXz8EUxahFi4aTTDffTu3ePsQsp4jSR6Q1CvY63E21VnIs8PWJDIaSKdJK9Ddgp0VoIlWaJOGEDKcda5Zkass_5BjzVlsg2npeuMe_WL_kWjLEeOXX9wiJx67lDS6savAWyxG_5NOYz2zbtqqHQS7cz4HnYAG83TRD8lun-Fa8bh6Z3yGEJ1lPHTd-Bx6anv8fO2HEFjvD8MEfs9fFhfv8czV6epvd3s6iVmewiJVAqCVUlhUi1qnIJE4EwkdqUSic6r7JUJgvEUpdCLyRiBVqNjRE4zsYiTUbseq8bHvjokboiWDfo3N5UMVEq0VLLAF4ewL6scVG0G1vDZlf8xBqAqwMAZMBVIQZj6ZcTKpRIvgBZa4qM</recordid><startdate>200102</startdate><enddate>200102</enddate><creator>TONUI, W. 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S</creatorcontrib><creatorcontrib>TURCO, S. J</creatorcontrib><creatorcontrib>GITHURE, J. I</creatorcontrib><creatorcontrib>KOECH, D. K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>East African medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TONUI, W. K</au><au>MBATI, P. A</au><au>ANJILI, C. O</au><au>ORAGO, A. S</au><au>TURCO, S. J</au><au>GITHURE, J. I</au><au>KOECH, D. K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transmission blocking vaccine studies in leishmaniasis : I. Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis</atitle><jtitle>East African medical journal</jtitle><addtitle>East Afr Med J</addtitle><date>2001-02</date><risdate>2001</risdate><volume>78</volume><issue>2</issue><spage>84</spage><epage>89</epage><pages>84-89</pages><issn>0012-835X</issn><coden>EAMJAV</coden><abstract>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. To assess the level of inhibition of promastigote development and gut morphology in infected Phlebotomus duboscqi sandflies fed on different groups of BALB/c mice immunised with rgp63, lipophosglycan (LPG) or their cocktail and whole parasite antigens prepared from L. major culture-derived promastigotes. BALB/c mice were immunised adequately with Leishmania major-derived antigens namely, crude whole parasite (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 L. major were later allowed to feed on immunised animals, interrupted and allowed to continue feeding on infected animals for an equal amount of time until they became fully engorged. The sandflies were maintained on apples as a carbohydrate source in an insectary maintained at a temperature of 25 degrees 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 were all dissected on the sixth day post-feeding and examined for procyclics, nectomonads, haptomonads and metacyclic promastigote forms of Leishmania. Sandflies which had previously fed on WPA, LPG plus rgp63 cocktail and LPG-immunised mice showed the lowest infection rates compared to control sandflies fed on saline immunised mice (p &lt; 0.05). A significant number of procyclic promastigotes, the first developmental form of the parasite in culture as well as in the sandfly was observed in sandflies which fed on LPG-immunised mice (p &lt; 0.05). 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 (p &lt; 0.05). 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 cause 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. This study has shown that immune-mediated transmission blocking may be applied to Leishmania infections. Based on observation of the procyclic promastigotes, 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.</abstract><cop>Nairobi</cop><pub>Kenya Medical Association</pub><pmid>11682952</pmid><doi>10.4314/eamj.v78i2.9094</doi><tpages>6</tpages></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Antibodies, Protozoan - blood
Biological and medical sciences
Disease Models, Animal
Drug Evaluation, Preclinical
Epidemiology. Vaccinations
General aspects
Glycosphingolipids - immunology
Infectious diseases
Insect Vectors - parasitology
Leishmania major - immunology
Leishmaniasis, Cutaneous - blood
Leishmaniasis, Cutaneous - immunology
Leishmaniasis, Cutaneous - parasitology
Leishmaniasis, Cutaneous - prevention & control
Leishmaniasis, Cutaneous - transmission
Medical sciences
Metalloendopeptidases - immunology
Mice
Mice, Inbred BALB C
Phlebotomus - parasitology
Protozoan Vaccines - immunology
Tropical medicine
title Transmission blocking vaccine studies in leishmaniasis : I. Lipophosphoglycan is a promising transmission blocking vaccine molecule against cutaneous leishmaniasis
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