Search

Background. Recombination technology can be used to create live attenuated respiratory syncytial virus (RSV) vaccines that contain combinations of known attenuating mutations. Methods. Two live attenuated, recombinantly derived RSV vaccine candidates, rA2cp248/404ΔSH and rA2cp248/404/1030ΔSH, were evaluated in 31 adults and in 95 children ≥6 months old. rA2cp248/404/1030ΔSH was subsequently evaluated in 44 infants 1–2 months old. These vaccine candidates share 4 attenuating genetic elements and differ only in a missense mutation (1030) in the polymerase gene. Results. Both vaccines were highly attenuated in adults and RSV-seropositive children and were well tolerated and immunogenic in RSV-seronegative children. Compared with that of rA2cp248/404ΔSH, replication of rA2cp248/404/1030ΔSH was restricted in RSV-seronegative children (mean peak titer, 104.3 vs. 102.5 plaque-forming units [pfu]/mL), indicating that the 1030 mutation had a potent attenuating effect. Although rA2cp248/404/1030ΔSH was well tolerated in infants, only 44% of infants who received two 105.3-pfu doses of vaccine had detectable antibody responses. However, replication after administration of the second dose was highly restricted, indicating that protective immunity was induced. At least 4 of 5 attenuating genetic elements were retained in recovered vaccine viruses. Conclusions. rA2cp248/404/1030ΔSH is the first RSV vaccine candidate to be sufficiently attenuated in young infants. Additional studies are needed to determine whether rA2cp248/404/1030ΔSH can induce protective immunity against wild-type RSV. [ABSTRACT FROM AUTHOR]

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 PW3-cp4S vaccines were combined in a dose of 105 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-2481404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-2481404 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: This study examined the transmissibility between young children of an intranasally administered live attenuated human parainfluenza virus type 3 (HPIV3)-cp45 vaccine candidate. Methods: Eighty subjects were enrolled in playgroups among whom there was at least one infected vaccinee in close contact with a seronegative placebo recipient over 21 days without a confounding infection with wtHPIV3. Following vaccination viral cultures were obtained on nine occasions to detect shedding and transmission of HPIV3cp45. Serum antibody titers were measured before and 7 weeks after vaccination. Results: No child fulfilled the criteria for transmission of HPIV3cp45 giving a risk of transmission of 0.04 (95% CI 0.01–0.19), hence establishing that HPIV3cp45 is less infectious than wtHPIV3 and risk of transmission is not a limitation to further clinical development of this vaccine candidate. [Copyright &y& Elsevier]