Phase 1 Study of the Safety and Immunogenicity of a Live, Attenuated Respiratory Syncytial Virus and Parainfluenza Virus Type 3 Vaccine in Seronegative Children

Background: Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are important causes of lower respiratory tract illness and hospitalization in young children. Currently, there is no licensed vaccine against RSV or PIV3. Methods: In this randomized, phase 1, double-blind, placebo-controlled, dose-escalating study, 49 healthy RSV/PIV3-seronegative children 6 to < 24 months of age were randomized 2: 1 to receive 3 doses (at 10(4), 10(5), or 10(6) median tissue culture infective dose [TCID(50)]) of MEDI-534 (a live, attenuated RSV/PIV3 chimeric virus vaccine candidate) or placebo at 2-month intervals. Solicited adverse events (SEs) and unsolicited adverse events (AEs) were recorded during days 0 to 28 after each dose. Nasal wash samples were collected 3 times (days 7-10, 12-18, and 28-34) after each dose and at unscheduled illness visits. Blood for antibody response was collected at baseline and 28 days after each dose. Subjects were followed for 180 days after the last dose or to the end of the RSV season. Results: Overall, there was no difference in the incidence of SEs and AEs between the RSV/PIV3 vaccine and placebo arms. Runny/stuffy nose was the most commonly reported SE. Medically attended lower respiratory illness rates were balanced between treatment arms, and there was no evidence of enhanced RSV disease or vaccine-related serious AEs. Vaccine virus was detected in most vaccinees on days 7 to 10 after dose 1 in a dose-dependent manner. Seroresponse to RSV and PIV3 was highest in subjects receiving the 10(6) dosage. Conclusions: The safety profile and vaccine take as measured by shedding and/or seroresponse in this RSV/PIV3-seronegative pediatric population support the continued development of this RSV/PIV3 pediatric vaccine candidate.