Live attenuated vaccines against influenza; an historical review

Live attenuated vaccines administered directly to the respiratory tract off er the promise of providing more effective immunity against influenza than subunit or split inactivated vaccines. Evidence has accumulated in recent y ears that immunological responses relevant to both the prevention of and re covery from influenza are brat induced by natural infection. The ease with which the genes of influenza viruses reassert when two or more viruses infe ct a single cell has been exploited as a means of rapidly producing attenua ted vaccines. Donor strains that have been shown by extensive testing to be fully attenuated are used to co-infect cells with contemporary epidemic st rains to produce reassortants with the required degree of avirulence and th e surface antigens of the epidemic strain. Reassortants prepared from cold- adapted mutants of both influenza A and B viruses have been widely shown fr om 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. (C) 2001 Elsevier Science Ltd. All rights: reserved.