Systematic evaluation of in vitro and in vivo adventitious virus assays for the detection of viral contamination of cell banks and biological products.

Viral vaccines and the cell substrates used to manufacture them are subjected to tests for adventitious agents, including viruses, contaminate. Some of the compendial methods (in vivo and in vitro in cell culture) were established in the mid-20th century. These methods have not been subjected to current assay validation, as new methods would need to be.

The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines.

Early in the development of respiratory syncytial virus (RSV) vaccines severe disease occurred in children after receipt of formalin-inactivated RSV vaccine. Continuing efforts to develop an appropriately attenuated and immunogenic live RSV vaccine have given opportunities to assure that live vaccines are safe through surveillance of children after vaccination. In the present study, the rate of RSV-associated upper respiratory tract illness in 388 children was lower in RSV vaccinated children than in controls (14% versus 20% in a 6-24 month old group and 16% versus 25% in infants).

Comparison of results of detection of rhinovirus by PCR and viral culture in human nasal wash specimens from subjects with and without clinical symptoms of respiratory illness.

Human rhinoviruses (HRV) cause acute upper respiratory illness. The frequency of HRV-associated illnesses appears greater when PCR assays are used to detect rhinoviruses. The present study performed PCR-based detection of HRV upon entry of subjects into respiratory syncytial virus and parainfluenza type 3 vaccine trials when subjects were symptom-free and upon subsequent development of clinical symptoms of respiratory illness during the trial.

The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans.

Background: Respiratory syncytial virus (RSV) is targeted for vaccine development, because it causes severe respiratory tract illness in the elderly, young children, and infants. A primary strategy has been to derive live attenuated viruses for use in intranasally administered vaccines that will induce a protective immune response. In the present study, the NS2 gene, whose encoded protein antagonizes the host's interferon- alpha / beta response, was deleted from RSV vaccine candidates by use of reverse genetics.

Genetic stability determinants of temperature sensitive, live attenuated respiratory syncytial virus vaccine candidates.

An intranasally delivered, live attenuated, temperature sensitive (ts) respiratory syncytial virus vaccine candidate, rA2cp248/404/1,030DeltaSH, exhibits a low level of genetic instability in clinical studies, in contrast to the relatively high stability of two similar candidates, cpts248/404 and rA2cp248/404DeltaSH. The latter strains, containing two ts mutations (248ts and 404ts), are partially growth restricted at 37 degrees C, whereas, rA2cp248/404/1,030DeltaSH contains an additional ts mutation (1,030ts) that increases attenuation and partially restricts virus growth at 35 degrees C. Since the maximum human airway temperature is 35.