Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine

Learn more about:
Related Clinical Trial
Transcriptomic Responses for the Identification of Pathogens Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana Non-inferiority and Safety Study of EuTCV Compared to Typbar-TCV in Healthy 6 Months-45 Years Aged Participants Commercial Typhoid Tests Validation Trial Commercial Typhoid Tests Validation WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study The Azithromycin and Cefixime Treatment of Typhoid in South Asia Trial (ACT-South Asia Trial) Phase 4 Study To Assess The Safety Of Vivotif At Different Release Titers Among Travelers Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults Safety and Immunogenicity of Three Formulations of Vi-CRM197 Vaccine Against S. Typhi in Adults (18-40 Years Old) Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adult (18-40 Years Old) Effects of Aging on Primary and Secondary Vaccine Responses in a 15-Year Longitudinal Cohort Safety and Immunogenicity of Typhax, a Typhoid Vaccine Safety and Tolerability of Typhoid Conjugate Vaccine (EuTCV) in Healthy Adults Immune Equivalence Between Multi-dose and Single Dose Formulation of Vi-DT and Their Overall Safety (Phase III) Investigating Enteric Fever – Salmonella Typhi and Paratyphi Challenge Study Induction of Gut Permeability by an Oral Vaccine Studies of Immune Responses to Orally Administered Vaccines in Developing Country Long Term Protection by and Persistence of Vi Antibodies Induced by Vi-rEPA Conjugate Vaccines in Vietnamese Children Injected at 2-5 Years or at 5-8 Years of Age Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants Typhoid Fever: Combined vs. Single Antibiotic Therapy Vaccines Against Salmonella Typhi Immune Non-inferiority and Safety of a Vi-DT Typhoid Conjugate Vaccine Dose Ranging Study to Determine the Safety, Reactogenicity and Immunogenicity of Typhoid Fever Vaccine (Ty800) in Healthy Adult Subjects Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults CVD 909 Vi Prime Boost Study Gatifloxacin Versus Ceftriaxone in the Treatment of Enteric Fever Safety, Reactogenicity and Immunogenicity of Vi-DT;Typhoid Conjugate Vaccine Typhoid Conjugate Vaccine Introduction in Navi Mumbai, India Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi Study of a Single Dose of SP093 Typhoid Vi Polysaccharide Vaccine in Japanese Subjects Typhoid Conjugate Vaccine Trial Among Children Younger Than 2 Years in Ouagadougou, Burkina Faso Understanding Typhoid Disease After Vaccination Typhoid Vi Vaccine Effectiveness in Hechi, Guangxi, China Introduction of the Vi Polysaccharide Typhoid Vaccine in Hue City, Central Vietnam Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children Evaluation of the Vi Polysaccharide Vaccine Against Typhoid Fever Safety and Immunogenicity of a Vi-DT Typhoid Conjugate Vaccine Combined Vi Vaccination and Health Education Program on the Burden of Typhoid in Childhood Global Genomic and Proteomic Profiling of African Children With Typhoid Fever

Brief Title

Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine

Official Title

Salmonella Typhi Vi O-Acetyl Pectin-rEPA Conjugate Vaccine, Phase 1 Trial in Adults at NIH CC

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...
    

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 Phase

Phase 1

Study Type

Interventional




Condition

Typhoid Fever

Intervention

BB IND 6989


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

25

Start Date

January 9, 2006

Completion Date

September 17, 2008


Eligibility Criteria

        -  INCLUSION CRITERIA:

        To be eligible, volunteers must be 18 to 45 years old, who

          1. are not participating in or plan to participate in another research protocol during
             the next three months;

          2. have not been vaccinated against typhoid fever or had typhoid fever within the last 5
             years;

          3. are not regularly taking a prescription drug for chronic medical condition;

          4. have no history of allergy to fruit or fruit pectin;

          5. are not pregnant or intend to become pregnant during the study period of 6 months;

          6. 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.
      

Gender

All

Ages

18 Years - 45 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00277147

Organization ID

060070

Secondary IDs

06-CH-0070


Study Sponsor

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


Study Sponsor

, , 


Verification Date

September 17, 2008