This study requires collection of cord blood at the time of delivery and enrolment of healthy newborns within 24 hours of birth. Most study institutions being referral centres do not have a consistent relationship between a regular antenatal check-up and the mother reporting for delivery to the same institution. Taking consent during antenatal/pre-labour period does not work effectively in most situations. So a 3-stage process is planned to obtain a written informed consent for study participation:

Antenatal/Pre-labour period: The study team in paediatrics department will have a close liaison with the department of obstetrics. A trained study staff/counsellor will be available in the antenatal clinic to meet the expecting mothers during their 37 week or later visits. This study staff, besides the usual counselling, will explain to the expecting mother about the importance of vaccination for the new born baby and details of the vaccine study being undertaken in the institution. The staff will also inform that a small quantity of blood (about 3.0 ml) will be collected from the placental side of the umbilical cord after birth of the baby for regular tests on newborn and potentially for testing polio and pentavalent (DTwP-HepB-Hib) antibodies. The mother will be assured that she will be provided with complete details about the study again once the baby is born and that she and the family will have sufficient time and opportunity to decide whether or not she will accept her baby’s participation in the study. If not, no testing related to the study will be performed.

Oral consent for cord blood: Cord blood is routinely collected in some institutions for blood group testing and newborn baby screening. An oral consent will be taken from the parents/LAR for cord blood collection after informing them that the blood will also be used to test for polio antibodies if parents/LAR agrees for her baby’s participation in a polio vaccine study; which will be completely explained after the baby is born. If not, the collected blood will not be tested for polio and Pentavalent (DTwP-HepB-Hib) antibodies.

Written informed consent: All babies delivered in the study institution during the enrolment period will be assessed for the eligibility criteria. If a baby fulfils the eligibility criteria, a complete informed consent process will be followed as per the national regulatory requirement. The study staff will approach the parent/LAR only once the mother and baby are stabilized after delivery [usually 6-8 hours in a normal vaginal delivery and within 24 hours in lower segment caesarean section (LSCS)] and the mother is in a healthy frame of mind for this discussion as judged by the investigator. Parent/LAR will not be approached for consent if the woman had a difficult delivery, obstructed labour, LSCS if on account of fetal distress/abnormality, any significant postpartum complication or a stressful situation where, as judged by the investigator, the process may add to the stress. In addition to obtaining written informed consent, audio-visual recording of the informed consent process for each trial subject will be done including the procedure of providing information to parent/LAR and their understanding of the consent process. Such audio-visual recording and related documentation would be preserved for five years as per regulatory guidelines.

Study visits, procedures & follow up

Immediately after birth, 3.0 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 three study arms (A, B & C) as per the randomization envelopes A dose of bOPV or mOPV1 will be given within 24 hours of birth as per the study arm. Birth dose of OPV will be skipped in Arm C. Parents will be advised to avoid any other vaccine from centres other than the study site. For every study infant, an immunization card will be issued indicating the baby to be a study child and that all vaccinations will be advised and taken care of by the study investigator during this period. Date of next visit to the study site will be given to the parents when they bring the baby for the due procedures. Where the newborn is not eligible or parents do not consent to participate, the cord blood will be discarded as per usual hospital procedures.

To ensure a good follow up and compliance, complete address and contact details of the family will be recorded and verified before the mother and baby are discharged from the hospital. Reminder telephone contacts/ household visits will be arranged through a social worker a day before every subsequent visit at 6, 10, 14, 18 and 22 weeks.

At 6 and 10 week visits, a dose of the study vaccine will be administered as per the study arm. At 14 weeks, one millilitre (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 intramuscularly using AD syringe in the anterolateral side of the right thigh. At 18 weeks, 3.0 ml blood will be collected by venepuncture followed by a dose of IPV to infants in all the study arms. At week 22 one ml of blood will be collected from all infants across all the three arms

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. A dose of bOPV will be given to all study participants to compensate for any loss in type specific vaccination and will be referred to the routine vaccination program for the subsequent vaccination according to the national immunization schedule. Parents will be advised that their child should also receive additional OPV doses during the SIAs in their area.