Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children.

Human parainfluenza virus type 1 (hPIV-1) is the most common cause of laryngotracheobronchitis (croup), resulting in tens of thousands of hospitalizations each year in the United States alone. No licensed vaccine is yet available. We have developed murine PIV-1 (Sendai virus [SeV]) as a live Jennerian vaccine for hPIV-1. Here, we describe vaccine testing in healthy 3- to 6-year-old hPIV-1-seropositive children in a dose escalation study. One dose of the vaccine (5 × 10(5), 5 × 10(6), or 5 × 10(7) 50% egg infectious doses) was delivered by the intranasal route to each study participant. The vaccine was well tolerated by all the study participants. There was no sign of vaccine virus replication in the airway in any participant. Most children exhibited an increase in antibody binding and neutralizing responses toward hPIV-1 within 4 weeks from the time of vaccination. In several children, antibody responses remained above incoming levels for at least 6 months after vaccination. Data suggest that SeV may provide a benefit to 3- to 6-year-old children, even when vaccine recipients have preexisting cross-reactive antibodies due to previous exposures to hPIV-1. Results encourage the testing of SeV administration in young seronegative children to protect against the serious respiratory tract diseases caused by hPIV-1 infections.

Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks.

RATIONALE, AIMS, AND OBJECTIVES: Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. METHODS: A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. RESULTS: Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. CONCLUSIONS: The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings.