Typhoid FeverPhase 1NCT00277147
Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine
A Phase 1 study testing BB IND 6989 in people with Typhoid Fever, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Typhoid Fever
- What is being tested?
- BB IND 6989
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jan 2006to 17 Sep 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine, Phase 1 Trial in Adults at NIH CC
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.
Read more
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...
Read the detailed description
Typhoid fever remains a common, serious and increasingly difficult to treat disease in developing countries. Control measures, such as safe drinking water, and food, and effective sewage, are not likely to be available soon in many of these countries. In the early 1990's most Salmonella typhi from the Mekong Delta region were resistant to chloramphenicol and ampicillin and treatment required new antibiotics such as ciprofloxacin. Now, resistance of S. typhi has spread to ciprofloxacin.
There are three licensed vaccines for typhoid fever. The whole cell parenteral and the oral attenuated vaccines confer only incomplete immunity of limited duration and cannot be incorporated into the routine vaccination of infants. S. typhi capsular polysaccharide (Vi) is safe, easily standardized and only one injection confers about 70% immunity in individuals greater than 5 years of age for at least 3 years. Its immunogenicity is lesser in 2-4 year-olds and it does not elicit protective antibody levels in children less than 2 years-old. Vi does not elicit a booster response at any age (age-related T-cell independent antibody response).
The immunogenicity of Vi is improved by covalently binding it to a protein to form a conjugate. Vi conjugates were safe and more immunogenic than Vi in adults, in 5-14 year-olds and in children 2-4 year-olds, and showed 90% efficacy in the 2-5 year olds for 47 months.
O-acetyl pectin mimics the antigenic properties of Vi. Although not immunogenic alone, O-acetyl pectin when conjugated induces serum Vi antibodies with booster responses in mice and in guinea pigs albeit at slightly lower levels than Vi conjugates in mice. Double immunodiffusion against mouse anti-Vi revealed antigenic identity between O-acetyl pectin and Vi conjugates.
There are advantages to using pectin as the polysaccharide component of conjugate vaccines for typhoid. Pectin is abundant, has no LPS and requires a simple chemical modification to prepare its di-O-acetyl derivative. Our yields of O-acetyl pectin-rEPA were similar to those of Vi-rEPA. Because it may not be reliable to extrapolate data from animals to humans and especially to infants, we propose clinical evaluation of O-acetyl pectin bound to the recombinant protein A of Pseudomonas aeruginosa (rEPA).
- Conditions
- Typhoid Fever
- Being tested
- BB IND 6989
- Keywords
- Typhoid Fever, Immunogenicity, Safety, Vaccine, Conjugate, Healthy Volunteer
- Medical subject headings
- Typhoid Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BB IND 6989Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2006 (estimated)
- Study start9 Jan 2006
- Study completion17 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Typhoid FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 25 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00277147
- Sponsor's protocol ID
- 060070
- Other IDs
- 06-CH-0070
- Status last verified
- 17 Sep 2008
- First submitted
- 12 Jan 2006
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 7960137Kossaczka 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.
PubMed 9169736Murdoch 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.
PubMed 9652619Szu 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.
PubMed 24657719
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine, Phase 1 Trial in Adults at NIH CC
- ClinicalTrials.gov ID
- NCT00277147
- Acronym / sponsor ID
- 060070
- Conditions
- Typhoid Fever
- Keywords
- Typhoid Fever, Immunogenicity, Safety, Vaccine, Conjugate, Healthy Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 9 Jan 2006
- Study completion
- 17 Sep 2008
- First posted
- 13 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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...
Detailed description
Typhoid fever remains a common, serious and increasingly difficult to treat disease in developing countries. Control measures, such as safe drinking water, and food, and effective sewage, are not likely to be available soon in many of these countries. In the early 1990's most Salmonella typhi from the Mekong Delta region were resistant to chloramphenicol and ampicillin and treatment required new antibiotics such as ciprofloxacin. Now, resistance of S. typhi has spread to ciprofloxacin.
There are three licensed vaccines for typhoid fever. The whole cell parenteral and the oral attenuated vaccines confer only incomplete immunity of limited duration and cannot be incorporated into the routine vaccination of infants. S. typhi capsular polysaccharide (Vi) is safe, easily standardized and only one injection confers about 70% immunity in individuals greater than 5 years of age for at least 3 years. Its immunogenicity is lesser in 2-4 year-olds and it does not elicit protective antibody levels in children less than 2 years-old. Vi does not elicit a booster response at any age (age-related T-cell independent antibody response).
The immunogenicity of Vi is improved by covalently binding it to a protein to form a conjugate. Vi conjugates were safe and more immunogenic than Vi in adults, in 5-14 year-olds and in children 2-4 year-olds, and showed 90% efficacy in the 2-5 year olds for 47 months.
O-acetyl pectin mimics the antigenic properties of Vi. Although not immunogenic alone, O-acetyl pectin when conjugated induces serum Vi antibodies with booster responses in mice and in guinea pigs albeit at slightly lower levels than Vi conjugates in mice. Double immunodiffusion against mouse anti-Vi revealed antigenic identity between O-acetyl pectin and Vi conjugates.
There are advantages to using pectin as the polysaccharide component of conjugate vaccines for typhoid. Pectin is abundant, has no LPS and requires a simple chemical modification to prepare its di-O-acetyl derivative. Our yields of O-acetyl pectin-rEPA were similar to those of Vi-rEPA. Because it may not be reliable to extrapolate data from animals to humans and especially to infants, we propose clinical evaluation of O-acetyl pectin bound to the recombinant protein A of Pseudomonas aeruginosa (rEPA).
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BB IND 6989 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 7960137Szu 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.
- Background: PubMed 9169736Kossaczka 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.
- Background: PubMed 9652619Murdoch 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.
- Derived from this study: PubMed 24657719Szu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BB IND 6989 in people with Typhoid Fever, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00277147, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.