Inactivated Poliovirus Vaccine (IPV) With or Without E.Coli Double Mutant Heat-Labile Toxin (dmLT) Challenge Study in Healthy Adults
Condition: Polio
Intervention: Inactivated Poliomyelitis Vaccine (IPV); E.coli Double Mutant Heat-Labile Toxin (dmLT) (adjuvant); Bivalent Oral Polio Vaccine (bOPV)
Intervention description: 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.
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
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)
Masking description: The study vaccine for Groups 1 and 2 (IPV alone and IPV + dmLT) will be administered IM in a blinded fashion. An unblinded positive control group (Group 3) will be administered bOPV.
The unblinded Research Pharmacist will perform all preparations of the study product for Groups 1 and 2. Preparation of the study product and administration to the subjects will occur in separate locations to preserve the blinding of staff except for Research Pharmacist. The study subjects, the study personnel who perform study assessments after administration of study product, data entry personnel at the site, and laboratory personnel performing immunologic assays will be blinded to the treatment assignment.
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: inactivated polio vaccine (IPV); double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult male or female, ages 18-45, inclusive

          -  Healthy as defined by absence of clinically significant medical condition, either
             acute or chronic, as determined by medical history and clinical assessment

          -  History of prior receipt of at least 3 doses of IPV

          -  Willing and able to provide written informed consent and willing to comply with study
             requirements

          -  Intention to remain in the area during the study period

          -  If female and of childbearing potential, not breastfeeding and not pregnant (based on
             a negative serum pregnancy test at screening and negative urine pregnancy tests prior
             to vaccine administration and bOPV challenge), planning to avoid pregnancy until at
             least three months after bOPV challenge, and willing to use an adequate method of
             contraception consistently. Effective methods include intrauterine device or hormonal
             contraceptives (oral, injectable, patch, implant, vaginal ring). Women with credible
             history of abstinence or in monogamous relationship with a vasectomized partner are
             also eligible.

        Exclusion Criteria:

          -  History of receiving any OPV at any time

          -  Receipt of IPV in the last five years

          -  History of or planned household contact with an individual receiving OPV in prior 4
             weeks, or at any point during the study

          -  Regular contact with children younger than six months (and thus not yet fully
             vaccinated against polio) and immunocompromised individuals

          -  Presence of fever on the day of vaccination (oral temperature ≥ 38°C)

          -  Received an investigational product within 30 days prior to randomization or planning
             to participate in another research study involving investigational product during the
             conduct of this study

          -  Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal,
             gastrointestinal, hematological, endocrine, immunological, dermatological,
             neurological, cancer or autoimmune diseases) as determined by medical history and/or
             physical examination that would compromise the participant's health or is likely to
             result in nonconformance to the protocol or would interfere with the evaluation of
             responses according to the opinion of the investigator

          -  History of allergic disease or known hypersensitivity to any component of the study
             vaccine

          -  History of anaphylactic reaction

          -  Receipt of any immunoglobulin therapy and/or blood products in the last 6 months or
             planned administration during the study period

          -  History of chronic administration (defined as more than 14 days) of immunosuppressant
             medications, including oral steroids, parenteral steroids, or high-dose inhaled
             steroids (> 800 μg/day of beclomethasone dipropionate or equivalent), in the last 6
             months to either the study subject or their close household contacts (those on nasal
             or topical steroids may be permitted to participate in the study)

          -  Symptoms of an acute self-limited illness, such as an upper respiratory infection or
             gastroenteritis, including a temperature ≥ 38.0°C, within the 7 days prior to study
             vaccines administration

          -  Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen
             (HBsAg) or hepatitis C virus (HCV) antibody

          -  Clinically significant screening laboratory value

          -  History of receipt of experimental E. coli, enterotoxigenic E. coli (ETEC) labile
             toxin (LT), or cholera vaccines or live E. coli or Vibrio cholerae challenges.

          -  Receipt of any licensed vaccine within 28 days before enrollment in this study or
             plans to receive any licensed vaccine between enrollment and 28 days after the bOPV
             challenge

          -  History of alcohol or drug abuse in the last 5 years

          -  Any condition that in the opinion of the investigator would pose a health risk to the
             subject if enrolled, or could interfere with the evaluation of the study vaccine