Comparative evaluation of immunogenicity and reactogenicity of bivalent oral poliovirus vaccine (bOPV) and trivalent oral poliovirus vaccine (tOPV) in the standard EPI schedule, with or without inactivated polio vaccine (IPV) administration at DTP3 contact: A randomized controlled trial

Comparative evaluation of immunogenicity and reactogenicity of bivalent oral poliovirus vaccine (bOPV) and trivalent oral poliovirus vaccine (tOPV) in the standard EPI schedule, with or without inactivated polio vaccine (IPV) administration at DTP3 contact.

The primary endpoint is seroconversion 28 days after 4 doses of bOPV compared to 4 doses of tOPV given in the routine immunization schedule.

The secondary endpoints are:

·         Seroconversion after one dose of IPV added to the tOPV or bOPV at 14 weeks (DPT3 contact) in the EPI schedule

·         Rapid boosting between 18 and 19 week visit to assess priming following the first dose of IPV (only in the bOPV + IPV arm)

·         Seroconversion after two doses of IPV added to the bOPV in the EPI schedule (only in the bOPV + IPV arm)

·         Boosting of antibody titres to any of the three poliovirus types by IPV, one or two doses

·         Comparing shedding of virus in the tOPV only, tOPV with IPV and bOPV with IPV arms after mOPV2 challenge at 18 weeks

·         Detecting any interference on the immunological endpoints accepted for clinical protection due to concomitant administration of IPV and pentavalent vaccine

Safety:•          To monitor and evaluate adverse events (AEs) following vaccine administration.

Study visits, procedures & follow up

Immediately after birth, 3-3.5 ml. cord blood will be collected. Newborn babies fulfilling eligibility criteria and whose parents have provided informed consent will be assigned in to one of the 5 study arms (A-E) as per the randomization list. A dose of tOPV or bOPV will be given within 24 hours of birth as per the study arm.  Where the newborn is not eligible or parents do not consent to participate, the cord blood will be discarded as per usual hospital procedures.

 At 6 and 10 week visits, a dose of the study vaccine will be administered as per the study arm. At 14 weeks, 1 ml. blood will be collected from each study participant by venepuncture followed by administration of vaccine/s as per the study arm. IPV will be given in addition to the tOPV/bOPV in the arms B, D, E as per the study arm. IPV will be given intramuscularly using AD syringe in the anterolateral side of the right thigh. At 18 weeks, 3-3.5 ml. blood will be collected by venepuncture from infants in all the study arms.

In arms A-D a stool sample will be collected at week 18, followed by administration of a challenge dose of mOPV2/tOPV except in arm C, where instead IPV will be administered IM  to compensate for the loss of type 2 vaccination. After this, a stool sample from each infant in arms A-D will be collected after 7 days (week 19) and 28 days (week 22). Arm E will have a second dose of IPV at 18 weeks, followed by blood sample, 1 ml. each at 19 and 22 weeks. In arm C, a second  dose IPV will be given at 22 weeks to compensate for the type 2 vaccination.

The study subjects will continue getting other (than polio) EPI vaccines concurrently. BCG and HepB will be given at birth as per EPI recommendation. Instead of DPT, these infants will be given pentavalent vaccine (DTP + Hep B + Hib) at 6, 10 and 14 weeks.

After having fulfilled the study requirements at 22 weeks, infants will exit the study, and will be referred to the routine vaccination program