TABLE 9.
Human challenge studies with enterotoxigenic Escherichia colia
| Challenge strain(s) | No. of volunteers | Purpose of study | Institution(s) | Reference |
|---|---|---|---|---|
| B2C, B7A | 24 | Establish ETEC as a cause of diarrhea | CVD and WRAIR | DuPont, 1971 (904) |
| 214-4 | 17 | Establish ST as a virulence factor | CVD | Levine, 1977 (905) |
| H10407 | 13 | Role of CF antigens in pathogenesis and immunity | University of Texas Medical School | Evans, 1978; Satterwhite, 1978 (906, 907) |
| B7A, E2528-C1 | 29 | Capacity of prior infection to protect from homologous or heterologous challenge | CVD | Levine, 1979 (908) |
| H10407, 214-4, TD255-C4 | 13 | Explore whether person-to-person transmission of ETEC can occur | CVD | Levine, 1980 (909) |
| TD255-C4, 214-4, B7A | 48 | Capacity of Lactobacillus to prevent diarrhea in volunteers after challenge with ETEC strains | CVD | Clements, 1981 (910) |
| H10407, B7A | 47 | Compare two antibiotics for treatment of diarrhea in ETEC-challenged volunteers | CVD | Black, 1982 (911) |
| H10407 | 26 | Evaluate a candidate vaccine antigen, somatic pili, for protection from disease in ETEC-challenged volunteers | CVD | Levine, 1982 (912) |
| H10407 | 16 | Evaluate bismuth subsalicylate for protection from diarrhea in ETEC-challenged volunteers | University of Texas Medical School | Graham, 1983 (913) |
| H10407, H1765 | 11 | Evaluate purified CFs as candidate vaccine antigens for protection from disease in ETEC-challenged volunteers | University of Texas Medical School | Evans, 1984 (914) |
| E24377A | 14 | Evaluate CS1 and CS3 colonization factors as antigens for protection from disease in ETEC-challenged volunteers | CVD | Levine, 1984 (915) |
| E24377A | 6 | Evaluate fimbriae antigens as vaccines | CVD | Levine, 1986 (916) |
| H10407 | 14 | Evaluate whole-inactivated ETEC vaccines for protection from challenge | University of Texas Medical School | Evans DG, 1988; Evans DJ, 1988 (917, 918) |
| H10407 | 20 | Protection by milk immunoglobulin concentrate against ETEC challenge | University of Maryland School of Medicine | Tacket, 1988 (919) |
| E24377A | 10 | Vaccination with CF encapsulated in microspheres, followed by challenge with ETEC | University of Maryland School of Medicine | Tacket, 1994 (920) |
| H10407 | 10 | Milk immunoglobulin with activity against CF antigens can protect from challenge | University of Maryland School of Medicine | Freedman, 1998 (921) |
| E24377A | 10 | Milk immunoglobulin does not protect from challenge when administered with a standard meal | University of Maryland School of Medicine | Tacket, 1999 (922) |
| B7A, H10407 | 32 | Pathogenicity of ETEC expressing CFA/I or CS6 in human volunteers, and capacity of ciprofloxacin to resolve symptoms of disease and prevent shedding | U.S. Army Medical Research Institute of Infectious Diseases | Coster, 2007 (923) |
| E24377A | 20 | Protective efficacy of transcutaneous immunization with ETEC LT in a challenge study | JHU and Iomai | McKenzie, 2007 (924) |
| E24377A | 16 | Efficacy of live-attenuated vaccine strain PTL-003 in protection from challenge | JHU and Acambis | McKenzie, 2008 (925) |
| LSN03-016011/A, WS0115A, DS26-1 | 38 | Experimental challenge with ETEC expressing CFs CS17 and CS19 | JHU and NMRC | McKenzie, 2011 (302) |
| LSN0-016011/A | 36 | Protective efficacy of anti-CS17 bovine colostrum passively administered to volunteers | JHU and NMRC | Savarino, 2019 (926) |
| H10407 | 45 | Dose de-escalation study for ETEC challenge strain H10407 | JHU and Gothenburg University | Harro, 2011 (301) |
| H10407 | 30 | Examine lower challenge doses in an effort to refine the model | JHU and PATH | Chakraborty, 2018 (298) |
| H10407 | 36 | Protective efficacy of ACE527 plus dmLT | JHU and PATH | Harro, 2019 (284) |
| TW10598 | 30 | Develop a new ETEC challenge strain for use in vaccine studies | University of Bergen | Skrede, 2014 (303) |
| TW11681 | 27 | Develop a new ST-producing challenge strain for use in vaccine studies | University of Bergen | Sakkestad, 2019 (297) |
| TW10722 | 21 | Develop a new ST-producing challenge strain for use in vaccine studies | University of Bergen | Sakkestad, 2019 (305) |
| B7A | 30 | Protective efficacy of bovine IgG antibodies against CS6 expressing E. coli passively administered to volunteers | JHU and NMRC | Talaat, 2020 (927) |
a
CF, colonization factor; CS, coli surface antigen; CVD, Center for Vaccine Development, University of Maryland; dmLT, double-mutant heat-labile toxin; E. coli, Escherichia coli; ETEC, enterotoxigenic Escherichia coli; IgG, immunoglobulin G; JHU, Johns Hopkins University; LT, heat-labile toxin; NMRC, U.S. Naval Medical Research Center; ST, heat-stable toxin; WRAIR, Walter Reed Army Institute of Research.