Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Abstract

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987. In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP. BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees. This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.

Keywords: Clinical trials; Influenza; Live attenuated influenza vaccine; Pandemic preparedness; Potentially pandemic viruses; Preclinical studies; Seasonal vaccine; Technology transfer.

Fig. 1

Antibody and cell-mediated immune responses to pandemic LAIVs in clinical trials. (A) Immune responses after dose 1; (B) Immune responses after two doses of the vaccine. Cal/09 H1N1pdm: A/17/California/2009/38 (H1N1); t/Turkey H5N2: A/17/turkey/Turkey/05/133 (H5N2) LAIV; mal/NL H7N3: A/17/mallard/Netherlands/00/84 (H7N3) LAIV; HAI – hemagglutination inhibition; MN – microneutralization; CMI – cell-mediated immune response. † MN and serum IgA tests were not performed for Cal/09 H1N1pdm LAIV. ‡ Only antibody immune responses are included in calculations because only a small proportion of subjects was tested for CMI.