Prospects of a living attenuated vaccine against influenza

Living attenuated vaccines offer the promise of providing more effective immunity against influenza than inactivated vaccines. However, the development of such vaccines presents unique problems, because influenza A viruses undergo frequent antigenic change and are highly infectious. Ideally, a living vaccine should produce substantial immunity to the disease from a single dose administered in the form of nose drops. The vaccine should be suitably attenuated, with attenuation being determined by in vitro markers which allow the ready detection of revertants to virulence. The only practical approach is to use a thoroughly accredited master strain which can be recombined with a contemporary virulent strain to produce an attenuated recombinant having the surface antigens of the contemporary strain. Of the master strains currently being developed, temperature-sensitive (ts) and cold-adapted (ca) mutants appear to have the greatest promise.