<span class="paragraphSection"><div class="boxTitle">Background</div>Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt.<div class="boxTitle">Methods</div>We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28; serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion or a ≥4-fold rise in antibody titer. The noninferiority limit was 10%. The secondary end point was safety, assessed by the number and intensity of adverse reactions.<div class="boxTitle">Results</div>A total of 503 of 534 enrolled participants (94.2%) completed all study requirements. Twenty-eight days after the first dose, 94.8%, 98.0%, and 98.0% of fIPV recipients had an immune response to poliovirus types 1, 2, and 3, respectively, compared with 98.1% (<span style="font-style:italic;">P</span> = .06), 98.0% (<span style="font-style:italic;">P</span> = 1.00), and 99.2% (<span style="font-style:italic;">P</span> = .45) in the IPV arm. Noninferiority was achieved on days 7, 28, and 56 for all serotypes. No serious adverse events were reported.<div class="boxTitle">Conclusion</div>fIPV induced similar boosting immune responses, compared with full-dose IPV. This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation.<div class="boxTitle">Clinical Trials Registration</div>ACTRN12615000305527.</span>
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