CVD 909 Vi Prime Boost Study
Condition: Typhoid Fever
MeSH terms: Typhoid Fever
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to see if giving a typhoid vaccine by mouth (an
      experimental vaccine, CVD 909) before giving a vaccine shot (Typhim Vi) will result in a
      better immune response than giving Typhim Vi vaccine by itself. Another purpose is to see
      whether CVD 909 is safe. Typhim Vi has been shown to be safe and effective in preventing
      typhoid fever in older children and adults, but it does not work in children under age 2.
      Scientists at the University of Maryland think that young children could respond to Typhim Vi
      if they were given a dose of the other typhoid vaccine by mouth before they are given the
      Typhim Vi shot. Twenty-eight healthy adult volunteers, ages 18-40 years, will take part in
      this study. Study participation will last for up to 63 weeks, but most of the study visits
      will be in the first 6 weeks. Blood samples will be collected approximately 13 times. Four
      stool samples will be collected. Some volunteers may be followed for an additional 4 years.
    

Detailed description: 
      This is a phase I, randomized, double-blind, heterologous prime-boost study of the safety and
      immunogenicity of Vi polysaccharide typhoid vaccine after priming by live, attenuated oral
      Vi+ Salmonella Typhi strain CVD 909. The primary study objective is to determine the phase 1
      safety of the prime-boost regimen of priming with CVD 909, a live attenuated Vi+ S. Typhi
      strain, followed by boosting with licensed parenteral Vi polysaccharide vaccine in healthy
      adult volunteers. The secondary objective is to compare the immunogenicity of licensed
      parenteral Vi polysaccharide vaccine in volunteers primed with a single oral dose of CVD 909
      and in volunteers who are not primed with the oral vaccine. The outcome measures of interest
      are the seroconversion rate and titer of serum IgG anti-Vi antibodies, the timing of
      development and longevity of serum anti-Vi antibodies, the subclasses and avidity of
      antibodies developed, and the memory B and T cell responses elicited. The following
      immunologic outcome measures will be sought: rate and timing of seroconversion in each study
      arm after receiving Vi polysaccharide and analysis of immunoglobulin subclasses and avidity.
      This will assess the presence of priming and the rapidity of the anamnestic response. A
      successful priming would accelerate the response to the boost (Day 7 after Vi vaccine), and
      this response is expected to be more balanced, inducing both Th1/Th2-type immunity evidenced
      by the induction of both IgG1 and IgG2; geometric mean titer (GMT) of serum IgG anti-Vi
      antibodies on Days 7, 14, 21, and 35 post-Vi (Days 28, 35, 42, and 84 of the study). This
      will assess magnitude of response (another measure of priming); GMT of serum IgG Vi antibody
      in each study arm at multiple later time points up to 1 year after receiving parenteral Vi
      (week 55 of the study). This will assess the quality and duration of the antibodies; and
      peripheral blood mononuclear cells will be collected to measure cytokine production and
      cytotoxic T lymphocyte (CTL) activity, as well as the induction and maintenance of B and T
      cell memory responses and homing potential of antibody secreting cells (ASC) and T cells
      depending on cell numbers. Twenty-eight healthy adult volunteers, 18-40 years of age and from
      the Baltimore community, will be recruited to participate in this study, which will be
      conducted at the Center for Vaccine Development (CVD), University of Maryland School of
      Medicine. The volunteers will be randomized to receive either 5x10^9 colony forming units of
      CVD 909 with buffer or buffer placebo alone. Three weeks later, all volunteers will receive
      25 micrograms (0.5 ml) of licensed purified Vi polysaccharide vaccine by the intramuscular
      route. Blood for serum and antibody secreting cell responses to Vi, S. Typhi LPS, and O
      antigen will be drawn before and after the Vi boost. The patient participation duration is up
      to 63 weeks, with the option for prolonged immunologic follow-up for 4 additional years.
    

Intervention name(s): CVD 909; Placebo; Vi Polysaccharide
Intervention type(s): Biological; Drug; Biological
Intervention description(s): 5 X 10^9 CFU of oral S. Typhi vaccine strain CVD 909 with buffer administered on Day 0.; Buffer placebo administered on Day 0.; 25 micrograms (0.5 ml) of licensed purified Vi polysaccharide vaccine on Day 21.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Salmonella, vaccine, typhoid fever, S. Typhi