Immunogenicity of Intramuscular Inactivated Poliovirus Vaccine
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Study type: Interventional
Phase: Phase 3

Summary: 
      This study will be an open-label phase III randomized clinical trial comparing different
      combinations and regimens of polio vaccines. The trial will compare one and two doses of IPV
      administered at 6 weeks or 14 weeks or 6 and 14 weeks of age. All participants will also
      receive bOPV at 6, 10 and 14 weeks of age.
    

Detailed description: 
      Oral poliovirus vaccines are live attenuated viral vaccines and 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 similar 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 WPV2 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 bivalent OPV (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 OPV types starting with the
      switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV). In November
      2013, SAGE recommended that countries that introduce at least one dose of IPV in the routine
      immunization program should administer the first dose of IPV at ≥14 weeks of age. In
      countries with routine immunization schedule of 6, 10 and 14 weeks of age or 2, 3 and 4
      months of age, IPV would then be added to the DTP3 visit for children on schedule or
      administered at the first immunization visit at 14 weeks or later if children are off
      schedule. For countries with 2, 4 and 6 month schedule, IPV could be added either to DTP2 or
      DTP3 visit. SAGE also proposed that countries have the flexibility to consider alternative
      schedules including administering IPV earlier than 14 weeks of age or administer more than
      one dose of IPV.

      The principal objective of pre-eradication introduction of IPV is to mitigate the risk
      associated with an increased susceptibility to type 2 polioviruses when bOPV is introduced.
      Therefore, the objective is to achieve the highest possible type 2 population immunity with
      IPV, which is a product of the per dose immunogenicity of IPV and the coverage achieved by
      IPV at that vaccination visit in routine immunization.

      At present, no study has assessed immunological response against type 2 poliovirus of a
      single dose of IPV at 14 weeks of age, the SAGE recommended target age for IPV introduction.
      Furthermore, there is need to determine the immunological response with other potential
      alternatives for IPV introduction in routine immunization within the context of EPI schedule
      including immunological response with more than one dose of IPV. Also there is urgent need to
      document the immunogenicity of bOPV at 6, 10 and 14 weeks of age with IPV against type 1 and
      3 polioviruses.

      In this trial, the investigators are trying to determine the immunogenicity of alternative
      schedules of administering IPV other than the SAGE recommended schedule of IPV at 14 weeks of
      age. How does the immunogenicity of multiple doses of IPV at 6 and 14 weeks of age compare to
      only one dose at 14 weeks of age? How does IPV immunogenicity at 6 weeks of age compare to
      IPV at 14 weeks of age?

      It is well established that seroconversion with multiple doses of IPV is increased by larger
      interval between IPV doses. A study in Cuba reported a higher type 2 seroconversion (89% vs
      83%) with two doses of IPV administered 2 months apart (8 and 16 weeks of age) compared to
      three doses of IPV administered one month apart (6, 10 and 14 weeks of age). The proposed
      trial will compare 2 doses of IPV (at 6 and 14 weeks of age) to a single dose of IPV
      administered at either 6 or 14 weeks of age. This trial would not only assess type 2
      seroconversions with IPV but also determine priming against type 2 poliovirus with the
      different proposed IPV schedules. Additionally, all trial participants will receive bOPV at
      6, 10 and 14 weeks of age. This would permit the trial to determine type 1 and type 3
      seroconversions observed with the combination of bOPV and IPV.

      Setting: Study area The study will be conducted in a suburb of Dhaka in the area of Mirpur.
      Mirpur is one of the 14 Thanas of Dhaka city with a population of about one million in an
      area of 59 square kilometers. Mirpur Thana of Dhaka city is divided into 14 sections. The
      area is densely populated and is about 8 kilometres from icddr,b's Dhaka Hospital.
    

Intervention name(s): bOPV/IPV (6 weeks); bOPV/IPV (14 weeks); bOPV/IPV (6 & 14 weeks)
Intervention type(s): Biological; Biological; Biological
Intervention description(s): bOPV at 6, 10 and 14 weeks of age IPV at 6 weeks of age; bOPV at 6, 10 and 14 weeks of age IPV at 14 weeks of age; bOPV at 6, 10 and 14 weeks of age IPV at 6 and14 weeks of age
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Polio; Inactivated polio vaccine; IPV; oral polio vaccine