Progress has been made toward the development of a trivalent live attenuated virus vaccine consisting of (1) a respiratory syncytial virus (RSV) subgroup A component; (2) a RSV subgroup B component; and (3) a parainfluenza virus type 3 (PIV3) vaccine element. Recombinant chimeric RSV subgroup A and B viruses bearing more attenuating mutations than the A2cpts248/404 vaccine candidate, that previously have been shown to retain mild reactogenicity for the upper respiratory tract of seronegative pediatric subjects, are being evaluated in volunteers. Importantly, the vaccine candidate, rA2cpts248/404/1030 with a deletion of the SH gene, is replicating to lower titer in infants and young chldren than the cpts248/404 virus suggesting that it is more attenuated than cpts248/404. Studies with recombinant RSV subgroup B candidate vaccine viruses have been initiated this year. A live attenuated PIV3 candidate vaccine, JS cp45, produced by our CRADA partner, Wyeth-Lederle-Praxis, in qualified Vero cells is satisfactorily attenuated, phenotypically stable, poorly transmissible, and immunogenic in seronegative infants and children, as well as one month old infants. A high level of immunity to a second dose of vaccine was observed one month later, and only moderate immunity was seen when the second dose was given three months later. Phase II trials have almost been completed. A dengue virus vaccine candidate derived from cDNA containing a 30 base deletion in its 3'-noncoding region was evaluated in 20 seronegative adult volunteers and found to be highly attenuated, very immunogenic, and non-tranmissible to mosquitoes.A human papilloma virus type 16 virus-like particle vaccine was shown to be safe and highly immunogenic in adult seronegative volunteers and phase II trials have been initiated.
