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.

OBJECTIVE

To evaluate the safety, tolerability, immunogenicity, and viral shedding profiles of a recombinant, live, attenuated human parainfluenza virus type 3 (HPIV3) vaccine, rHPIV3cp45, 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 rHPIV3cp45 (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 rHPIV3cp45 in HPIV3-seronegative infants 6 to <12 months of age support further development of this vaccine.