Phase 1/2b Testing of the Sm-TSP-2 Schistosomiasis Vaccine in Uganda
Abstract
Background: Schistosomes (also called blood worms) are one of many types of worms that are found in areas of poverty, where freshwater sources are contaminated by human urine and feces. The worms cause a disease called Schistosomiasis. Schistosomiasis can lead to chronic and life-threatening diseases or cancers of the bladder, kidney, liver, or intestines. The goal of this proposal is to perform a clinical trial to test a new vaccine, called Sm-TSP-2. The Sm-TSP-2 vaccine is a product that teaches the body to recognize and fight shistosome worms, so as to prevent new infections. This study will test if the vaccine is safe and effective when tested in African adults in a region where the worm is common. In the first Phase I trial of healthy adults in the U.S., the vaccine was found to be safe and generated antibodies against the worm. A second Phase I trial will start in Brazil in an area where the schistosome worm is common. The next step in development of the vaccine is to test it in areas of Africa where infection with different strains (species) of the schistosoma parasite are common. Relevance to Topic Area: This application addresses the “Vaccine Development for Infectious Disease” Peer Reviewed Medical Research Program Topic Area and Area of Encouragement: development of a schistosomiasis vaccine to prevent U.S. Service members from becoming ill from the schistosome worms during deployments to areas of poverty around the world. Rationale for the Trial: Our research in the lab and in animal models leads us to think that the vaccine will protect against Schistosomiasis by causing the person’s immune system to create antibodies against the schistosome worm. The antibodies will be made in sufficient quantity to kill both adult and baby worms that have infected the person. Our specific goals are to: (1) assess the safety and immune responses to the Sm-TSP-2 vaccine in individuals living in an area of Uganda where the schistosome worm is common; (2) at 12 and 18 months after vaccination, to compare new worm infections in two groups: those who received the Sm-TSP-2 vaccine versus those who receive a control vaccine, the licensed Hepatitis B vaccine (HBV); and (3) assess blood samples taken from study subjects over the course of the study to look at cell-level responses to the vaccine. Study Design: The study will be done in two parts. Part A will be a randomized, double-blind Phase I trial in 90 healthy Ugandan adults aged 18-45 years. The study will test three doses (low, medium, high) of the vaccine, with or without AP 10-701 (AP 10-701 is an adjuvant, or substance that may help the human body make a stronger response to the vaccine). In each dose group of 30 people, 12 will receive the Sm-TSP-2 vaccine alone, 12 will receive the Sm-TSP-2 vaccine mixed with AP 10-701, and 6 will receive the control HBV. Subjects will receive three injections (in their deltoid arm muscle) at 2-month intervals over 4 months and will be followed for 9 months after the final injection. Part B will test the vaccine in a larger number of people, comparing 100 people vaccinated with Sm-TSP-2 to 100 people vaccinated with the HBV. The vaccine dose level to be tested in Part B will be chosen based on results of Part A. Part B subjects will receive three vaccine injections administered at 2-month intervals. After final vaccination, urine and stool samples will be collected at 12 and 18 months after the third injection to determine the rates of new schistosome worm infection. The primary endpoint of this study is to determine if vaccination prevents infection with the schistosome worm as determined by schistosome worm eggs found in feces or urine. Other outcomes include studying the antibody responses to Sm-TSP-2. In Parts A and B, people will be put in groups at random and will not know what vaccine or dose they received. Impact and Relevance to the U.S. Military: This project would have a significant impact on the
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810672
Entities
People
- David Diemert
Organizations
- George Washington University
- United States Army