Clinical Trial: Immunogenicity of Inactivated and Live Polio Vaccines
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Phase III Clinical Trial to Assess the Immunogenicity of a Sequential Dose of Fractional Inactivated Polio Vaccine (f-IPV) and Oral Polio Vacc
Brief Summary:
This study is an open-label phase III randomized clinical trial that would compare immunogenicity after receiving one of five different combinations of polio vaccines. Infants will be enrolled and randomized at 6 weeks of age to one of five different arms:
A) Three doses of trivalent oral poliovirus vaccine (tOPV) at 6, 10 and 14 weeks of age B) Three doses of bivalent OPV (bOPV) at 6, 10 and 14 weeks of age C) Two doses of intramuscular (IM) inactivated poliovirus vaccine (IPV) at 6 and 14 weeks of age D) Two doses of intra-dermal (ID) fractional IPV (f-IPV) at 6 and 14 weeks of age E) Sequential administration of ID f-IPV at 6 and 14 weeks of age with bOPV at 10 weeks of age To assess the immunogenicity of each study vaccine and vaccination schedule, antibody titers against poliovirus types 1, 2 and 3 will be determined in sera extracted from blood collected before (at 6 weeks of age) and after receiving 3 doses of study vaccine (18 weeks of age). Seroconversion will be defined as a titer 4-fold higher than the expected fall in maternally derived antibodies, assuming a half-life of 28 days. The initial antibody titer at 6 weeks of age will be used as the starting point for the expected decline in maternal antibody.
This study will compare the immunogenicity of:
- Sequential dose of intra-dermal f-IPV and bOPV to bOPV alone administered at 6, 10 and 14 weeks of age
- tOPV to bOPV administered at 6,10 and 14 weeks of age
- IM IPV to ID f-IPV administered at 6 and 14 weeks of age The answer to these questions will guide the global polio eradication program in designing new routine immunization schedule for children that eliminates the risks of paralysis due to vaccine derived poli
Detailed Summary:
Global polio eradication initiative (GPEI)
In 1988, the World Health Assembly adopted the resolution of polio eradication by 2000. This launched the Global Polio Eradication Initiative (GPEI), spearheaded by World Health Organization (WHO), Rotary International, US Centers for Disease Control and Prevention (CDC) and United Nations Children's Emergency Fund (UNICEF). The major strategies to achieve polio eradication included: 1) provision of 3-4 doses of tOPV to young infants through routine immunization programs; 2) provision of additional doses to all children < 5 years of age through immunization campaigns (supplementary immunization activities or SIAs); 3) surveillance for all cases of acute flaccid paralysis in children <15 years of age; and 4) mop-up immunizations campaigns following the detection of poliovirus circulation.
OPV was the vaccine of choice for polio eradication due to its low cost, ease of administration, ability to induce intestinal immunity and community spread to aid in induction of immunity.
Limitations of trivalent oral polio vaccine (tOPV)
tOPV is a mixture of all three types of polioviruses and there is interference among the strains during intestinal replication. Type 2 especially interferes with uptake of types 1 and 3. tOPV has higher seroconversion rates in industrialized countries compared to that in developing countries. A study conducted in Brazil and Gambia reported tOPV seroconversion rates of 85% for Type 1, 94% for type 2 and 68% for Type 3 with three doses of tOPV. Compared to monovalent OPVs, trivalent OPV has lower seroconversion rates. To address concerns of lower efficacy of tOPV for type 1 and type 3 compared to monovalent vaccines, monovalent vaccines were re-introduced in t
Sponsor: Centers for Disease Control and Prevention
Current Primary Outcome: Seroconversion [ Time Frame: Change in antibody titers at 18 weeks of age compared to 6 weeks of age ]
The primary analytical approach will be intention-to-treat analysis on enrolled participants who have serological results available on blood specimens collected at 18 weeks of age.
Reciprocal antibody titers of at least 1:8, the lowest detectable titer, is considered to indicate seropositivity with regards to the presence of poliovirus neutralizing antibodies. Seroconversion is defined as either seronegative participants (<1:8 titers) who become seropositive (≥1:8) or participants who demonstrate a 4-fold change in titers between two specimens, e.g. a change from 1:8 to 1:32. To compare the immunogenicity across study arms, the investigators will compare the proportion of participants who seroconvert by 18 weeks of age. Chi-square tests will be used to test the statistical significance among seroconversion rates across study arms.
Original Primary Outcome: Same as current
Current Secondary Outcome: Poliovirus shedding in stool [ Time Frame: At 19 weeks of age ]
Stool specimens collected a week after a challenge dose of tOPV will be analyzed to determine poliovirus shedding. By study arm the investigators will compare proportion of participants shedding poliovirus overall and by type of poliovirus. The investigators will also evaluate quantitative viral shedding (viral titers) and compare these results by study arm.
Original Secondary Outcome: Same as current
Information By: Centers for Disease Control and Prevention
Dates:
Date Received: March 12, 2013
Date Started: November 2012
Date Completion:
Last Updated: January 7, 2014
Last Verified: March 2013
