Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine

NCT00277147 | Completed Phase 1

• 2 other identifiers: 06007006-CH-0070
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate a new (conjugate) vaccine for typhoid fever, which remains a serious disease especially difficult to treat in developing countries. Salmonella typhi, the bacteria causing typhoid fever, have become resistant to several antibiotics increasing the difficulty of treating the disease. The disease may have serious complications effecting bones, brain, and intestines, with permanent injury or death. Methods to control typhoid fever, such as a sanitary water and food supply, along with effective sewage treatment, are not likely to be available soon in those countries. NIH scientists developed a vaccine called Vi, made of a polysaccharide (a chain of linked sugars) from the surface of Salmonella typhi, the bacteria that cause typhoid fever. It has been approved by the World Health Organization and is licensed in 94 countries. It is effective in adults but not in young children. Clinical trials have shown that chemically binding the Vi to a protein to form a "conjugate vaccine" has improved and extended its efficacy to children (conjugate vaccines to other bacteria, notably meningitis causing bacteria have been used extensively and successfully). Now NIH scientists have developed another vaccine for typhoid fever - using a polysaccharide from fruit, known as pectin. The pectin has been chemically treated so that it resembles Vi. The treated pectin, O-acetyl pectin, is bound to a protein; exoprotein A, (rEPA). The result is a conjugate, as was formed for Vi. Similarly to the Vi conjugate it induces antibodies against Salmonella typhi in laboratory animals. If the O-acetyl pectin conjugate proves successful, it will be evaluated in children ages 5 to 14 years old and in infants, toward using it with routine vaccines for infants. Volunteers ages 18 to 45 who do not have an allergy to fruit pectin and who have not been vaccinated against nor had typhoid fever within the last 5 years may be eligible for this study. Volunteers will undergo several tests at their first visit to the clinic for this study. A blood sample (about 2/3 of an ounce) will be taken to test for HIV, hepatitis B and C, complete blood count, liver functions, blood chemistry and pregnancy in women of childbearing age. The blood sample will also be tested for antibodies to Vi, rEPA (the protein of the conjugate), and pectin. There will also be a urine collection for testing. If the laboratory tests are acceptable, volunteers will be asked to return to the clinic on a...

Conditions

Typhoid Fever

Keywords

Typhoid Fever; Immunogenicity; Safety; Vaccine; Conjugate; Healthy Volunteer

Interventions

BB IND 6989 DRUG

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible, volunteers must be 18 to 45 years old, who
• are not participating in or plan to participate in another research protocol during the next three months;
• have not been vaccinated against typhoid fever or had typhoid fever within the last 5 years;
• are not regularly taking a prescription drug for chronic medical condition;
• have no history of allergy to fruit or fruit pectin;
• are not pregnant or intend to become pregnant during the study period of 6 months;
• Whose HIV, HBsAg and HCV tests must be found negative and laboratory tests of liver function, blood chemistry, complete blood count and urine must show no clinically significant abnormality or pregnancy.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Szu SC, Bystricky S, Hinojosa-Ahumada M, Egan W, Robbins JB. Synthesis and some immunologic properties of an O-acetyl pectin [poly(1-->4)-alpha-D-GalpA]-protein conjugate as a vaccine for typhoid fever. Infect Immun. 1994 Dec;62(12):5545-9. doi: 10.1128/iai.62.12.5545-5549.1994.

  PMID: 7960137 BACKGROUND

• Kossaczka Z, Bystricky S, Bryla DA, Shiloach J, Robbins JB, Szu SC. Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker. Infect Immun. 1997 Jun;65(6):2088-93. doi: 10.1128/iai.65.6.2088-2093.1997.

  PMID: 9169736 BACKGROUND

• Murdoch DA, Banatvaia N, Bone A, Shoismatulloev BI, Ward LR, Threlfall EJ. Epidemic ciprofloxacin-resistant Salmonella typhi in Tajikistan. Lancet. 1998 Jan 31;351(9099):339. doi: 10.1016/s0140-6736(05)78338-0. No abstract available.

  PMID: 9652619 BACKGROUND

• Szu SC, Lin KF, Hunt S, Chu C, Thinh ND. Phase I clinical trial of O-acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine. Vaccine. 2014 May 7;32(22):2618-22. doi: 10.1016/j.vaccine.2014.03.023. Epub 2014 Mar 21.

  PMID: 24657719 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 12, 2006
• First Posted: January 13, 2006
• Study Start: January 9, 2006
• Study Completion: September 17, 2008
• Last Updated: July 2, 2017

Record last verified: 2008-09-17

Locations

US (1)