Monovalent Oral Poliovirus Vaccine Type 1 Intestinal and Humoral Immunity Study

Phase 4CompletedNCT03722004

Centers for Disease Control and Prevention1,256 enrolled

Overview

This is an open-label phase IV randomized clinical trial that will assess intestinal and humoral immunity among infants who receive a combination of monovalent oral poliovirus vaccine type 1 and fractional dose of inactivated poliovirus vaccine, monovalent oral poliovirus vaccine type 1 only, and bivalent oral poliovirus vaccine only.

The risk for circulating vaccine-derived poliovirus (cVDPV) will increase in the years immediately after the cessation of oral poliovirus vaccine (OPV) use in routine immunization programs. Judicious use of type-specific monovalent OPV (mOPV) will be necessary for outbreak response to prevent further paralytic infections and transmission; however, data on the intestinal and humoral immunity induced by mOPV1 are very limited. Furthermore, the additional benefit of fractional dose inactivated poliovirus vaccine (fIPV) on type 1 immunity when given with mOPV1 is unclear. Data on intestinal and humoral immunity of mOPV type 1 (mOPV1) and combination use of mOPV1 and fractional dose of IPV (fIPV) are urgently needed and would be used to inform guidelines for type 1 outbreak response in a post-OPV world. In the immediate future, a strategy of shifting from bivalent OPV (bOPV) to mOPV1 as part of supplemental immunization activities in endemic countries is under consideration but data on intestinal and humoral immunity to support this change does not exist. This trial is designed to address both areas in which data are lacking. Healthy infants 5 weeks of age will be enrolled at two study clinics in Dhaka, Bangladesh, and randomized to one of four study arms: mOPV1 + fIPV at 6 weeks, mOPV1 + fIPV at 14 weeks, mOPV1 only, and bOPV only. Infants will be followed-up until 18 weeks of age by clinic and household visits. Blood and stool specimens will be collected to test for vaccine response (humoral immunity) and vaccine virus shedding (intestinal immunity).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

1,256

Conditions

Poliomyelitis

Interventions

mOPV1BIOLOGICAL

Monovalent oral poliovirus vaccine type 1 is a type-specific, live, attenuated oral poliovirus vaccine that protects against poliovirus type 1.

bOPVBIOLOGICAL

Bivalent oral poliovirus vaccine is a live, attenuated oral poliovirus vaccine that protects against poliovirus types 1 and 3.

fIPVBIOLOGICAL

Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.1 milliliter (mL) dose (fractional) by intradermal injection in lieu of the full 0.5mL dose that is given intramuscularly.

Eligibility

Sex: ALLMin age: 35 DaysMax age: 41 DaysHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy infants 5 weeks of age (range: 35-41 days). * Parents that consent for participation in the full length of the study. * Parents that are able to understand and comply with planned study procedures. Exclusion Criteria: * Parents and infants who are unable to participate in the full length of the study. * A diagnosis or suspicion of immunodeficiency disorder either in the infant or in an immediate family member. * A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of fIPV or collection of blood by venipuncture. * Evidence of a chronic medical condition identified by a study medical officer during physical exam. * Infection or illness at the enrolment visit (i.e., 5 weeks of age) that a study medical officer judges would prevent the start of study activities at 6 weeks of age (i.e., blood collection and vaccination). * Receipt of any polio vaccine (OPV or IPV/fIPV) before enrolment based upon documentation or parental recall. * Known allergy/sensitivity or reaction to polio vaccine, or its contents. * Infants from multiple births. Infants from multiple births will be excluded because the infant(s) who is/are not enrolled would likely receive OPV through routine immunization and transmit vaccine poliovirus to the enrolled infant. * Infants from premature births (\<37 weeks of gestation).

Locations (1)

icddr,b study clinics (Mirpur and CTU Dhaka)

Dhaka, Bangladesh

Outcomes

Primary Outcomes

Vaccine response

Dichotomous (yes/no) variable defined as participants who are either seronegative (\<1:8 titers) at baseline who become seropositive (≥1:8) after vaccination (seroconversion) or participants who demonstrate a four-fold rise in titers after vaccination between two specimens, e.g. a change from 1:8 to 1:32, after adjusting for expected decay in maternal antibodies. Antibody titers at 6 weeks of age will be the starting point for the expected decline in maternal antibodies, assuming at half-life of 28 days.

Time frame: Measured four weeks after administration of study vaccine(s). Vaccine response will be measured at 10 weeks, 14 weeks, and 18 weeks of age after 1, 2, and 3 doses of OPV, respectively.

Vaccine virus particles

Presence or absence of vaccine virus particles in stool specimens.

Time frame: Measured 7 and 14 days after administration of the study vaccine. For Arms B, C, and D, this will be after administration of the first mOPV1 or bOPV dose. For Arms A, B, and C, this will be after the mOPV1 challenge dose at 14 weeks of age.

Secondary Outcomes

Reciprocal antibody titers

Variable of the observed reciprocal antibody titer results.

Time frame: Measured four weeks after administration of study vaccine(s). Vaccine response will be measured at 10 weeks, 14 weeks, and 18 weeks of age after 1, 2, and 3 doses of OPV, respectively.

Data from ClinicalTrials.gov

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