Abstract
BACKGROUND: Human parainfluenza virus type 3 (HPIV3) is an important yet underappreciated cause of lower respiratory tract illness in children, and a licensed vaccine is not yet available. METHODS: A live-attenuated investigational HPIV3 vaccine virus designated rcp45 was derived from cDNA by using reverse genetics. rcp45 is genetically similar to the biologically derived cp45 vaccine virus and contains all of the known attenuating mutations of cp45, but has the advantage of a short, well-characterized passage history. We evaluated the tolerability, infectivity, and immunogenicity of 2 intranasal doses of rcp45 administered 4 to 10 weeks apart in a placebo-controlled, double-blind trial. A total of 45 infants and children between 6 and 36 months of age participated in this study. Tolerability and antibody responses to vaccine or placebo were assessed in all recipients. Infectivity was assessed by quantitation of vaccine virus shedding in a subset of vaccinated children. RESULTS: rcp45 was well tolerated and highly infectious in HPIV3-seronegative children. A second dose of vaccine administered 4 to 10 weeks after the first dose was restricted in replication and did not boost serum antibody responses. The stability of 9 cp45 mutations, including the 6 major attenuating mutations, was examined and confirmed for viral isolates from 10 children. CONCLUSIONS: The level of attenuation and immunogenicity of cDNA-derived rcp45 is comparable to what was previously observed with the biologically derived cp45 vaccine, and preliminary data suggest that the attenuating mutations in this vaccine virus are genetically stable. Continued clinical development of rcp45 is warranted.