A randomized, double-blind, placebo-controlled, phase 1/2a study of the safety and immunogenicity of a live, attenuated human parainfluenza virus type 3 vaccine in healthy infants

Abstract

Objective To evaluate the safety, tolerability, immunogenicity, and viral shedding profiles of a recombinant, live, attenuated human parainfluenza virus type 3 (HPIV3) vaccine, rHPIV3 cp45, in healthy HPIV3-seronegative infants 6 to <12 months of age. Methods In this double-blind, multicenter study, subjects were randomized 2:1 to receive a 10 5 TCID 50 dose of rHPIV3 cp45 ( n = 20) or placebo ( n = 10) at enrollment and at 2 and 4 months after the first dose. Blood for evaluation of antibody to HPIV3 was collected at baseline and approximately 1 month after each dose. Solicited adverse events (SEs) and unsolicited adverse events (AEs) were collected on days 0–28 after each dose. Nasal wash samples for vaccine virus shedding were collected 3 times after each dose (7–10, 12–18, and 28–34 days post dose) and at unscheduled illness visits. Subjects were followed for 180 days after the last dose. Results Vaccine virus was shed by 85% of vaccine recipients after dose 1, by 1 subject after dose 2, and was not shed by any subject after dose 3. The highest titer of shed virus was detected on day 7 after dose 1. The attenuation phenotype and the genotype of the vaccine virus were stable in shed virus. Seroresponse (≥4-fold rise in HPIV3 antibody from baseline) occurred in 61% of subjects after dose 1 and in 77% after dose 3. Either seroresponse or shedding occurred in 95% of vaccine subjects. Adverse events were similar in vaccine and placebo recipients. Conclusion The safety, shedding, and immunogenicity profiles of rHPIV3 cp45 in HPIV3-seronegative infants 6 to <12 months of age support further development of this vaccine. ClinicalTrials.gov Identifier: NCT00508651.