Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae PspA
Condition: Pneumonia
MeSH terms: Pneumonia; Pneumonia, Pneumococcal
Study type: Interventional
Phase: Phase 1

Summary: 
      In this Phase I clinical study, three recombinant, avirulent Salmonella Typhi (RASV) strains
      each expressing the Streptococcus pneumoniae surface protein, PspA, will be compared as live
      biological vaccine vectors to evaluate safe and tolerable, single, oral dose levels in adult
      subjects.
    

Detailed description: 
      The use of attenuated Salmonella strains that are unable to cause clinical disease but
      trigger a self-limiting infection leading to stimulation of protective immunity presents an
      attractive alternative to killed and subunit vaccines. Live, attenuated Salmonella strains
      have been shown to be excellent carriers, or vectors, for prokaryotic or eukaryotic antigens,
      being able to stimulate strong systemic and local immune responses against the expressed
      antigens. Three Salmonella Typhi strains have been engineered to express a gene encoding the
      alpha-helical domain of the Streptococcus pneumoniae surface protein, PspA, and will serve as
      live biological vaccine vectors in the proposed clinical trial to evaluate maximum safe and
      tolerable single dose levels after their oral administration to subjects. In this Phase I
      study, healthy young adults 18-40 years of age will participate in a dose escalating, dose
      sequential study divided into four Arms to receive doses of 10^7, 10^8, 10^9 and 10^10 CFU.
      Each Arm (1-4) will consist of 3 groups of 5 subjects per group to receive a single oral dose
      of one of three recombinant attenuated S. Typhi vaccine vectors producing the pneumococcal
      antigen PspA. Each group per Arm will receive the same dose of one of the three vaccines for
      a total of 60 subjects (15 subjects per dose-escalating Arm, 3 groups per Arm, 5 subjects per
      group). Subject participation lasts 6 months after receiving the oral vaccine dosage with
      approximately the first 12-15 days (study Days 0-14) in confinement. Release criteria include
      2 negative blood cultures in a row through study Day 7 (inpatient monitoring for 8 days) and
      2 negative stool cultures in a row through study Day 5. The objectives of the study are 1) to
      evaluate maximum safe tolerable single dose levels of the three recombinant attenuated S.
      Typhi vaccine vectors using dose-escalation, dose-sequential studies in healthy adult
      subjects, and 2) to evaluate immunogenicity of the three recombinant attenuated S. Typhi
      vaccine vectors with regard to their abilities to induce mucosal and systemic antibody
      responses to the S. pneumoniae PspA and S. Typhi antigens. The vaccines are not anticipated
      to prevent disease. Although the immune responses generated by the vaccine vectors may confer
      some degree of protection against future infection with S. pneumoniae and S. Typhi, such
      protection is incidental. It is not the goal of this study to develop or test either a
      pneumonia or typhoid vaccine, but to select the S. Typhi vector that provides optimal
      delivery of the PspA antigen in a safe and immunogenic manner.
    

Intervention name(s): Salmonella Typhi-vectored pneumonia vaccine; Salmonella Typhi-vectored pneumonia vaccine; Salmonella Typhi-vectored pneumonia vaccine; Salmonella Typhi-vectored pneumonia vaccine
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): Liquid, oral dosage administered once at 10^7 CFU in 10 mL phosphate-buffered saline; Liquid, oral dosage administered once at 10^8 CFU in 10 mL phosphate-buffered saline; Liquid, oral dosage administered once at 10^9 CFU in 10 mL phosphate-buffered saline; Liquid, oral dosage administered once at 10^10 CFU in 10 mL phosphate-buffered saline
Other intervention name(s): RASV strains; RASV strains; RASV strains; RASV strains
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Salmonella Typhi; pneumonia; oral; vaccine