ABSTRACT
The authors wish to make the following correction to this paper [...].
ABSTRACT
Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequality, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although chemotherapy is capable of reducing morbidity in humans, rapid re-infection demonstrates that the impact of drug treatment on transmission control or disease elimination is marginal. In addition, despite more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic, open knowledge innovation that has successfully completed phase I and phase IIa clinical trials, with Phase II/III trials underway in the African continent, to be followed by further trials in Brazil. The discovery and experimental phases of the development of this vaccine gathered a robust collection of data that strongly supports the ongoing clinical phase. This paper reviews the development of the Sm14 vaccine, formulated with glucopyranosyl lipid A (GLA-SE), from the initial experimental developments to clinical trials including the current status of phase II studies.
ABSTRACT
The Sm14 antigen of Schistosoma mansoni was cloned and expressed in Mycobacterium bovis BCG as a fusion with the Mycobacterium fortuitum beta-lactamase protein under the control of its promoter, pBlaF*; the protein was localized in the bacterial cell wall. The rBCG-Sm14 strain was shown to be relatively stable in cultured murine and bovine monocytes in terms of infectivity, bacterial persistence, and plasmid stability. The immunization of mice with rBCG-Sm14 showed no induction of anti-Sm14 antibodies; however, splenocytes of immunized mice released increased levels of gamma interferon upon stimulation with recombinant Sm14 (rSm14), indicating an induction of a Th1-predominant cellular response against Sm14. Mice immunized with one or two doses of rBCG-Sm14 and challenged with live S. mansoni cercaria showed a 48% reduction in worm burden, which was comparable to that obtained by immunization with three doses of rSm14 purified from Escherichia coli. The data presented here further enhance the status of Sm14 as a promising candidate antigen for the control of schistosomiasis and indicate that a one-dose regimen of rBCG-Sm14 could be considered a convenient means to overcome many of the practical problems associated with the successful implementation of a multiple-dose vaccine schedule in developing countries.
Subject(s)
Carrier Proteins/immunology , Helminth Proteins/immunology , Membrane Transport Proteins , Mycobacterium bovis/genetics , Schistosoma mansoni/immunology , Schistosomiasis mansoni/prevention & control , Vaccines, DNA/immunology , Animals , Antibodies, Helminth/blood , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cattle , Cells, Cultured , Fatty Acid Transport Proteins , Female , Helminth Proteins/genetics , Helminth Proteins/metabolism , Interferon-gamma/biosynthesis , Mice , Mice, Inbred BALB C , Monocytes , Mycobacterium fortuitum/enzymology , Mycobacterium fortuitum/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Schistosoma mansoni/growth & development , Schistosoma mansoni/pathogenicity , Schistosomiasis mansoni/parasitology , Vaccines, DNA/administration & dosage , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
Fasciola hepatica is the causative agent of fasciolosis in many areas in America, Europe, Africa, Asia and Australia. There is an urgent need for improved methods to control the parasite's transmission. We describe the use of an experimental vaccine based on a recombinant antigen cloned from another parasite, Schistosoma mansoni (Sm14), that induces high levels of cross protection in mice against both S. mansoni and F. hepatica. Sheep and mice vaccinated with Sm14 were significantly protected against challenge infection with metacercariae of Fasciola hepatica and were completely free of the histopathological hepatic damage related to liver fluke infection. The vaccine will provide a valuable new tool to aid in transmission control of this economically important disease.
Subject(s)
Antigens, Helminth/immunology , Carrier Proteins/administration & dosage , Fasciola hepatica/immunology , Fascioliasis/prevention & control , Helminth Proteins/administration & dosage , Membrane Transport Proteins , Schistosoma mansoni/immunology , Vaccination , Animals , Carrier Proteins/immunology , Fascioliasis/immunology , Fatty Acid Transport Proteins , Helminth Proteins/immunology , Immunity, Active , Liver/pathology , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Sheep , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/geneticsABSTRACT
The migration of larval Schistosoma mansoni was tracked by means of autoradiographic analysis in naive rabbits percutaneously exposed to L-(**75 Se) selenomethionine-labeled cercariae on serial intervals of 1, 2, 4, 6, 8, 10, 15, 20, 25, 30, 40 and 50 days post-infection. Autoradiographic foci were detected from the 1st day in the skin, up to the 15th day in the liver. Adult and mature worms were recovered either paired or not 60 days after infection, by perfusion of hepatic and mesenteric veins. Morphometric analysis under optical microscopy, showed that worms were within regular dimention limits as compared to adult worms harboured by other host species. These observations extend previous informations on the S. mansoni-rabbit association and clearly demonstrate the post-liver phase of S.mansoni life-cycle in this host
