Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune response but does not protect Syrian golden hamsters (Mesocricetus auratus) and BALB/c mice against Leishmania donovani

The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG) plus Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine candidate against visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster (Mesocricetus auratus) models was investigated. Following a triple vaccination with a total dose of 150 µI BCG plus 60 µg or 30 µg of LPG for hamsters and BALB/c mice respectively, there were no noticeable side effects both locally and systemically; implying that the molecule was safe at this dosage level. Vaccinated animals demonstrated an activation of both the humoral as well as cell-mediated responses to LPG, which correlated with resistance against the disease. Protection by LPG plus BCG, was however, poor as the remaining immunized animals showed disease progression leading to severity of the disease as illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters. These data nevertheless suggest that it may be rewarding to further evaluate the potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants, which may enhance its immunogenicity.The articles have been scanned with a HP Scanjet 8300; 600dpi, saved in TIFF format. Adobe Acrobat v.9 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.Intemational Society for Infectious diseases (lSID). Intemational Atomic Agency (IAEA). Kenya Medical Research Institute.mn201

TRANSMISSION BLOCKING VACCINE STUDIES IN LEISHMANIASIS: 11. EFFECT OF IMMUNISATION USING LEISHMANIA MAJOR DERIVED 63 KILODALTON GLYCOPROTEIN, LIPOPHOSPHOGLYCAN AND WHOLE PARASITE ANTIGENS ON THE COURSE OF L. MAJOR INFECTION IN BALBIC MICE

Background: Safe, effective and inexpensive vaccines may be the most practical tool for controlof any form of leishmaniasis. Leishmaniasis produces a state of pre-immunition which is theunderlying mechanism for prolonged immunity to re-infection. Low doses of parasites has beenshown to beable to induce protection in mice. It is not known, however, how immunesel-a froma susceptible host imrnunised with Leishmania-derived antigens when taken in by the sandflyaffects the development and the subsequent transmission of the parasite to naive hosts.Objective: To monitor the course of disease in BALBlc mice following challenge using L.rnajor infected P. duboscqi which had previously fed on immunised mice.Methods: BALBIc mice were immunised adequately withLeishrnania major-derived antigensnamely, crude whole parasite (WPA), recombinant 63 kilodalton glycoprotein (rgp63),lipophosphoglycan (LPG;) ancl a cocktail composed of rgp63 plus LPG antigens. Laboratoryreared Phlebotornus duboscqi sandflies, the natural vector for L. major were later allwwed tofeed on immunised animals, interrupted and allowed to continue feeding on infected animalsfor an equal amount of time until they became fully engorged. The sandflies were maintainedon apples as a carbohydrate source in an insectary maintained at a temperature of 2S°C and80% relative humidity. On the seventh day these sandflies were used to infect naivc B:ALB/c mice and the course of infection followed for a period of at least three months.Results: Mice infected usingsandflies which had previously fed on WPA or rgp63-immunizedmice showed disease exacerbation as the infection progressed, whereas those infected usingsandflies which had previously fed on LPG-immunised mice had the least lesion sizescompared to control mice infected using sandflies which had fed on saline immunised mice(p<0.05).Conclusions: Results from this study indicate that the course of L. major infection in BALBIc mice was dependent on the infective dose of parasites transmitted by the sandflies. R~:sultsfrom this study suggests that sub-infective doses of the parasite from sandflies previously fedon animals immunised with Leishmania-derived antigens needs to be evaluated for theirpotential in vaccine development against Leishmania infections