RECENT PROGRESS IN THE DEVELOPMENT AND ASSESSMENT OF LIVE ATTENUATED VACCINES Chairman: PROFESSOR

Temperature-sensitive (ts) recombinants of influenza A virus were evaluated for use in a live virus vaccine. Evidence from several sources suggested that the ts lesions were responsible for attenuation of these mutants. Specification of attenuation by defined genetic lesions which can be assayed for in the laboratory offers an advantage to the use of ts viruses for vaccination. This means that ts recombinants can be assessed for genetic stability during vaccine development, production and later during usage in man. One ts virus, influenza A/Hong Kong/68-ts-l[E], with a 38°C shut-off temperature, had the following properties desirable for a live virus vaccine: (1) satisfactory infectivity for seronegative (serum HI antibody titre < 1: 8) adults; (2) satisfactory attenuation for adults; (3) capacity to stimulate local and serum anti-haemagglutinin and anti-neuraminidase antibodies in seronegative volunteers; (4) stimulation of resistance to virulent, wild type virus; (5) relative genetic stability in vivo; (6) lack of communicability in man; (7) replication to high titre in avian leucosis virus-free eggs; and (8) localization of ts lesions to genes that do not code for the haemagglutinin and neuraminidase. The ts lesions of