Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children.

We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6-18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 10(5) plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine; 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/PV3 vaccine is feasible for simultaneous administration, and further studies are warranted.

Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old.

A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)-cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6-18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature > or =38 degrees C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a > or =4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1 : 25 in the vaccine group and <1 : 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial.

The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3-1cp45, is attenuated, immunogenic, and protective in African green monkeys.

A recombinant live-attenuated chimeric human parainfluenza virus type 1 (HPIV1) candidate vaccine was previously generated by replacing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein open reading frames (ORFs) of the HPIV3 candidate vaccine, rHPIV3cp45, with those of wild-type HPIV1. Previously, this recombinant chimeric virus, designated rHPIV3-1cp45, exhibited a greater level of the temperature sensitivity of replication in vitro and a greater level of attenuation of replication in the respiratory tract of immunized hamsters when compared to its HPIV3cp45 parent virus. In the present study, rHPIV3-1cp45 was evaluated for its level of attenuation and efficacy in African green monkeys (Cercopithecus aethiops), a primate in which both HPIV1 and HPIV3 wild-type viruses replicate efficiently. The rHPIV3-1cp45 candidate vaccine was as restricted in replication in the upper and lower respiratory tract as its thoroughly characterized rHPIV3cp45 parent indicating that the attenuating mutations present in the rHPIV3cp45 backbone specified an appropriate level of attenuation of rHPIV3-1cp45 for primates. The level to which rHPIV3-1cp45 replicated in the respiratory tract of African green monkeys was also sufficient to induce a strong immune response to HPIV1 and provided protection against challenge with wild-type HPIV1. These results provide a basis for further evaluation of this HPIV1 candidate vaccine in humans.