The purpose of this study is to evaluate the safety and tolerability of co-administration of nOPV1 + nOPV2 in infants, relative to those receiving monovalent nOPV vaccines alone and whether two and/or three doses of co-administered nOPV1 and nOPV2 are non-inferior to corresponding doses of nOPV1 alone and nOPV2 alone.

This is a randomized, double dummy, observer blind, active comparator-controlled study. The study population will comprise healthy infants randomized at 16 weeks of age equally across three study groups, nOPV1 only group (N=225), nOPV2 only group (N=225) and co-administered nOPV1+ nOPV2 group (N=225). The participants in the nOPV1 and nOPV2 groups will receive concomitant oral placebo (sterile water) to blind the study arms for parents.

Participants will be screened (screening period 10 weeks), randomized and administered the first dose of study vaccine(s) at 16 weeks of age. The second and third dose of study vaccine(s) will be administered at 20 and 24 weeks of age, respectively. Participants will be consented and screened at 6 weeks of age and receive their routine Expanded Program on Immunization (EPI) vaccines by the study team. For each group, blood will be collected for immunologic testing at 16 (baseline), 20, 24, and 28 weeks of age. Serum specimens will be tested for humoral responses to vaccination by measurement of serum neutralizing antibody (NAb) according to established World Health Organization (WHO) protocols. Stool samples will be collected at various timepoints to evaluate type-specific shedding of polio virus following vaccination.

Following vaccination, participants will be monitored for at least 30 minutes for any immediate adverse events (AEs). Reactogenicity (solicited AEs) will be assessed during the 7 days (day of vaccination and 6 following days) after each vaccination. Parents will be given a post-immunization memory aid to record any local and systemic solicited reactions. In addition, data for unsolicited AEs will be collected for 28 days (day of study vaccination and 27 following days) after each vaccination. Data for SAEs will be collected throughout the study period following vaccination.

Inclusion Criteria:

1. Healthy male or female infant 16 weeks (+ 7 days) of age, at the time of first study vaccination. Healthy as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment by the investigator.
2. Parent(s) willing and able to provide written informed consent prior to performance of any study-specific procedure.
3. Resides in study area and parent understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form (ICF) and assessment by the investigator).
4. Prior to study vaccination has received EPI vaccines as per the study EPI schedule and has received a single dose of IPV at 6 weeks (+7 days) of age.
5. Prior to study vaccination has received no doses of OPV, based upon no evidence of such vaccination per available documentation.
6. Parent agrees for participant to receive routine infant and childhood immunizations as per the approved protocol-adjusted schedule.

Exclusion Criteria:

1. Presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete age appropriate vaccination status (as per local guidelines) with respect to poliovirus vaccines at the time of study vaccine administration.
2. Member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous 3 months before study vaccine administration. Participants from household where a member received investigational nOPV3 vaccine will also be excluded from the study.
3. Low birth weight (LBW), defined as a birth weight of less than 2500 g (up to and including 2499 g) at the time of birth.
4. Premature birth (less than 37 weeks gestation).
5. From multiple births (due to increased risk of OPV transmissions between siblings).
6. Moderate or severe (grade ≥ 2) acute illness at the time of eligibility/first study vaccination - temporary exclusion. Note: Participants with mild (grade 1) acute illnesses may be considered eligible at the discretion of the investigator.
7. Presence of fever on the day of randomization/first study vaccination (axillary temperature ≥37.5˚C) - temporary exclusion.
8. Presence of abnormal vital signs (respiratory rate and/or heart rate) for age on the day of randomization/first study vaccination - temporary exclusion.
9. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin).
10. Any reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member. Topical and inhaled steroids are permitted.
11. Receipt of any immune-modifying or immunosuppressant drugs prior to the first study vaccine dose or planned use during the study of study participants or a household member. Topical and inhaled steroids are permitted.
12. Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection.
13. Presence of severe malnutrition (weight-for- length/height z-score <-3SD median [per WHO published child growth standards]) - temporary exclusion if marginal and subsequently gains sufficient weight to attain z-score ≥-3 SD.
14. Receipt of any investigational product prior to the first administration of study vaccine, or planned use during the study period.
15. Receipt of rotavirus vaccine within 2 weeks prior to first study vaccination.
16. Prior receipt of an investigational product containing poliovirus vaccine.
17. Receipt of transfusion of any blood product or immunoglobulins prior to the first administration of study vaccine or planned use during the study period.
18. Parent or participant has any condition that in the opinion of the investigator would increase the participant's health risks in study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments).