Live attenuated vaccines against influenza; an historical review.

Live attenuated vaccines administered directly to the respiratory tract offer the promise of providing more effective immunity against influenza than subunit or split inactivated vaccines. Evidence has accumulated in recent years that immunological responses relevant to both the prevention of and recovery from influenza are best induced by natural infection. The ease with which the genes of influenza viruses reassort when two or more viruses infect a single cell has been exploited as a means of rapidly producing attenuated vaccines. Donor strains that have been shown by extensive testing to be fully attenuated are used to co-infect cells with contemporary epidemic strains to produce reassortants with the required degree of avirulence and the surface antigens of the epidemic strain. Reassortants prepared from cold-adapted mutants of both influenza A and B viruses have been widely shown from clinical trials in both the United States and Russia over many years to be well tolerated in both adults and children and to be highly efficacious.