Use of temperature-sensitive and cold-adapted mutant viruses in immunoprophylaxis of acute respiratory tract disease.

Efforts currently are underway to develop mutations in the influenza A viral genome that will bring about a satisfactory level of attenuation and that can be identified by simple in vitro techniques. Two types of donor viruses that bear such mutations are being evaluated. One donor virus possesses temperature-sensitive (ts) mutations on the P1 and P3 genes, while the other donor bears both ts and cold-adaptation (ca) mutations. The mutant genes from these donors were transferred by gene reassortment to recombinant viruses bearing the surface antigens of new epidemic or pandemic viruses, and in every instance a satisfactory level of attenuation was achieved. However, genetic instability remains a formidable problem. Temperature-sensitive mutants of respiratory syncytial virus also have been evaluated for their usefulness in immunoprophylaxis of respiratory tract disease. Although the desired mutant has not been identified, some progress has been made.