Intestinal and Humoral Immunity of Sequential Polio Vaccination Schedules
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a phase IV open-label randomized clinical trial that will compare intestinal and
      humoral immunity in infants receiving inactivated poliovirus vaccine (IPV) and two or three
      doses of bivalent oral poliovirus vaccine (bOPV).
    

Detailed description: 
      The goal of polio vaccination is to protect the individual from paralytic disease (humoral
      immunity) and to prevent transmission of poliovirus (intestinal immunity). Inactivated
      poliovirus vaccine (IPV) induces humoral (systemic) immunity to all three types of poliovirus
      (1, 2 and 3), protecting individuals from developing paralytic polio when exposed to wild
      type poliovirus. However, it induces little intestinal immunity. Intestinal immunity inhibits
      poliovirus replication thereby reducing the quantity and duration of poliovirus excretion in
      stool. This is critical in preventing the spread of poliovirus to others.

      Oral polio vaccines are live attenuated vaccines and trivalent OPV (tOPV) is a mixture of
      poliovirus strains type 1, 2 and 3. Like IPV, OPV induces humoral immunity and is more
      effective than IPV at inducing intestinal immunity. In most developing countries, routine
      childhood immunization for poliovirus consists of three doses of tOPV at 6, 10 and 14 weeks
      of age and may also include a birth dose of tOPV.

      An important limitation is that the vaccine virus in OPV can mutate and acquire
      neurovirulence causing paralysis either due to vaccine-associated paralytic polio (VAPP) or
      due to circulating vaccine-derived polioviruses (cVDPVs), in which the attenuated vaccine
      virus not only acquires the ability to cause paralysis but can also circulate similarly to
      wild poliovirus (WPV). The potential of vaccine virus to acquire neurovirulence and cause
      paralytic poliomyelitis is incompatible with eradication of polio. Therefore, polio
      eradication will require eventual cessation of all OPVs.

      The last case of WPV type 2 was reported in 1999 in India. Type 2 vaccine virus in tOPV is
      most likely to cause cVDPVs and over 80% of cVDPVs over the past decade have been cVDPV2. Of
      the estimated 250-500 annual VAPP cases, almost 40% are due to type 2. Thus, with the
      eradication of WPV2 it is imperative to prioritize removal of type 2 containing OPV.

      The licensing and availability of bOPV containing type 1 and 3 offers the option of an OPV
      that does not contain OPV2. In April 2013, the Strategic Advisory Group of Experts on
      Immunization (SAGE) recommended phased cessation of OPVs starting with the switch from tOPV
      to bOPV. After the switch, bOPV is expected to be administered at 6, 10 and 14 weeks of age,
      the typical routine poliovirus immunization schedule in developing countries for tOPV.
      Additionally, at least one dose of IPV was recommended to prevent rapid rise in type 2
      susceptibility in the birth cohorts born after the switch to bOPV.

      The Global Polio Eradication Initiative (GPEI) has advocated for administration of at least
      one dose of IPV and delaying the dose to 14 weeks of age to decrease interference by maternal
      antibodies and provide the highest seroconversion possible with a single dose of IPV in the
      Expanded Program on Immunization (EPI) schedule. The GPEI position of introducing only one
      dose of IPV at 14 weeks of age is principally based on findings from a trial in Cuba that
      reported type 2 seroconversion of 63% with a single dose of IPV given at 16 weeks of age. The
      current schedule of Bangladesh is tOPV at 6, 10 and 14 weeks of age with IPV also at 14 weeks
      of age.

      As a result of the addition of IPV to the routine immunization schedule, children will
      receive four doses of the polio vaccine (three bOPV and one IPV) but are four doses
      necessary? Could IPV administered with a reduced number of bOPV doses still lead to
      protective levels of humoral and intestinal immunity? Previous studies in the US and UK
      suggest that two doses of OPV given with one or two doses of IPV induces protective levels of
      humoral and intestinal immunity comparable to three doses of tOPV. Furthermore, a recent
      study in Bangladesh found that there were no significant differences in type 1 or 3
      seroconversion proportions among children on a three-dose bOPV schedule versus a fractional
      IPV (f-IPV)/bOPV schedule (two f-IPV, one bOPV). Although there were significant differences
      in vaccine virus excretion among children who received only bOPV compared to f-IPV/bOPV to
      type 1 and 3, this difference could have been diminished if a second dose of bOPV was given
      instead of f-IPV .

      In addition, there has been interest in whether a VAPP-protective schedule could mount
      protective levels of immunity in individuals. A VAPP-protective schedule is the
      administration of IPV as the first dose of poliovirus vaccination. The risk of VAPP is
      highest with the first dose of OPV and diminishes with subsequent OPV administrations. There
      is no risk of VAPP when IPV is given as the first dose because the vaccine uses killed virus.
      The rationale behind the VAPP-protective schedule is that individuals would have prior
      exposure to types 1, 2, and 3 through IPV before their first bOPV administration, thereby
      decreasing the risk for VAPP.

      Investigators of this trial will assess if a reduced number of bOPV doses given with a dose
      of IPV confers a protective level of immunity against polio by examining the intestinal and
      humoral immunity induced by two different bOPV/IPV VAPP-protective sequential schedules among
      infants in Bangladesh. Specially, investigators will examine the proportion of seroconversion
      and vaccine virus excretion in children who receive an IPV dose at 6 weeks of age and bOPV at
      6, 10 and 14 weeks of age in comparison to children who receive an IPV dose at 6 weeks of age
      and bOPV only at 10 and 14 weeks of age.

      Setting: Mirpur is a suburb of Dhaka with a population of about one million in an area of 59
      square kilometers. Mirpur Thana of Dhaka city is divided into 14 sections. Mirpur is about 8
      kilometers from icddr,b's Dhaka Hospital.
    

Intervention name(s): bOPV (three dose); bOPV (two dose); IPV
Intervention type(s): Biological; Biological; Biological
Intervention description(s): bOPV administered at 6, 10, and 14 weeks of age.; bOPV administered at 10 and 14 weeks of age.; IPV administered at 6 weeks of age
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: polio; inactivated poliovirus vaccine; oral poliovirus vaccine; IPV; OPV