Inactivated Poliovirus Vaccine (IPV) With or Without E.Coli Double Mutant Heat-Labile Toxin (dmLT) Challenge Study in Healthy Adults
Condition: Polio
Study type: Interventional
Phase: Phase 1

Summary: 
      In this study, the safety and tolerability of inactivated polio vaccine (IPV) co-administered
      with dmLT will be assessed, as well as whether co-administration of dmLT with IPV enhances
      mucosal responses compared to those with IPV alone.
    

Detailed description: 
      A major component of the strategy aimed at worldwide eradication of polio advanced by the
      World Health Organization (WHO) is based on the replacement of oral polio vaccine (OPV) with
      IPV; however, IPV is not efficient in preventing person-to-person poliovirus transmission,
      particularly in settings of poor hygiene, due to limited impact on intestinal mucosal
      immunity compared to OPV. The addition of an adjuvant, in particular one that may direct the
      response towards mucosal homing may offset that deficiency.

      In this study, the safety and tolerability of IPV co-administered with dmLT will be assessed,
      as well as whether co-administration of dmLT with IPV enhances mucosal responses to
      polioviruses types 1, 2, and 3 in comparison with administration of IPV alone and provides
      greater mucosal immunity, assessed following oral bOPV challenge. The positive control arm
      (bOPV) is included in order to confirm the level of shedding observable following a dose of
      an oral vaccine known to develop intestinal immunity.
    

Intervention name(s): Inactivated Poliomyelitis Vaccine (IPV); E.coli Double Mutant Heat-Labile Toxin (dmLT) (adjuvant); Bivalent Oral Polio Vaccine (bOPV)
Intervention type(s): Biological; Biological; Biological
Intervention description(s): IMOVAX® Polio is a highly purified, inactivated poliovirus vaccine. Each 0.5 mL dose contains:
Type 1 (Mahoney) 40 D-antigen units
Type 2 (MEF1) 8 D-antigen units
Type 3 (Saukett) 32 D-antigen units; LT (R192G/L211A), or "dmLT," is a protein toxoid derived from wild-type enterotoxigenic Escherichia coli (ETEC) labile toxin (LT). The LT toxin has been shown to have inherent mucosal adjuvant properties for co-administered antigens and thus has potential as a mucosal adjuvant for different co-administered vaccines. LT has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites, which are critical for activation of the secreted toxin molecules.; Polio Sabin™ One and Three (oral) is a bivalent, live attenuated poliomyelitis virus vaccine of the Sabin strains Type 1 (LSc, 2ab) and Type 3 (Leon 12a, 1b), propagated in MRC5 human diploid cells.
Each dose (0.1 mL) contains not less than 10⁶ 50% cell culture infectious dose (CCID₅₀) of Type 1 and 10⁵·⁸ CCID₅₀ of Type 3.
Other intervention name(s): IMOVAX® Polio Vaccine; LT (R192G/L211A); Polio Sabin™ One and Three (Oral)
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will receive a single dose of licensed trivalent IPV, administered intramuscularly (IM), with or without dmLT, or bOPV, administered orally (PO). IPV or IPV + dmLT will be administered to groups of 30 participants each. Both participants and clinical staff will be blinded to group assignment (IPV alone vs IPV + dmLT). A positive unblinded control group will be included, composed of 20 participants receiving bOPV. One month (28 days) after receiving study vaccine, all participants will receive a standard oral dose of bOPV to assess relative impact of study vaccine on shedding of that challenge virus.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: inactivated polio vaccine (IPV); double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)