The Evolving History of Influenza Viruses and Influenza Vaccines

Claude Hannoun


Expert Rev Vaccines. 2013;12(9):1085-1094. 

In This Article

Early Influenza Vaccination

Louis Pasteur was responsible for the first known attempt to vaccinate with a live 'attenuated' viral strain. He had developed a method involving serial passages to alter a virulent wild-type rabies virus so that it lost its virulence and thus its pathogenic power. Smorodintseff in the USSR was the first in 1936 to attempt vaccination with a live influenza vaccine that had been passed about 30-times in eggs.[2] Smorodintseff reported that the modified virus caused only a barely perceptible, slight fever and that subjects were protected against reinfection. This level of attenuation was judged to be 'acceptable,' and therefore the attenuated virus was used for mass production of a live, attenuated vaccine that was widely used for factory workers. In principle, the trials were designed to assess vaccination in active working populations, with the goal of reducing absenteeism due to acute respiratory diseases. The reported results did not completely reflect reality because the evaluation methods used were not reliable and would not be considered to be acceptable today; both vaccinated and nonvaccinated subjects self-reported influenza episodes, with no control of the specificity of these reports. The conclusions drawn of good efficacy should, therefore, be interpreted with caution. The same subjective assessment methods were used for safety, and the vaccine was considered to be 'well tolerated.' There are no data for these vaccines in at-risk groups or frail/elderly subjects. This type of vaccine was widely used in USSR for more than 50 years, being administered to more than a billion subjects and was still being used until the end of the 20th century in Saint-Petersburg.[Smorodintseff,Pers. Comm.]

Since that time, several attempts have been made in other countries to develop new live-attenuated influenza vaccines; however, the unpredictability of influenza viruses remains a problem. Thus, although it is relatively easy to obtain less virulent viruses after several passages, as Smorodintseff did, these variants are not stable and they quickly recover their virulence, which precludes their use in vaccines. The structure of the genome of these attenuated viruses was determined and studies to assess the risk of reversion lead to the selection of strains that were sufficiently attenuated and stable to satisfy the necessary conditions to be used in a live-attenuated vaccine.[3] Results from clinical trials demonstrated the efficacy of these vaccines to prevent primo-infection by the attenuated strain that is necessary for the vaccine to work, particularly in younger subjects who did not have natural immunity.[4] The available data suggest that these vaccines do not provide good protection in elderly/adults subjects.[5] Live-attenuated vaccines are more complicated to use than other types of vaccines and a number of problems were identified: instability of the attenuation, risk of recombination with wild strains, pre-existing immunity preventing infection by the vaccine strain and instability of the live preparations. These problems have been resolved and a vaccine has now been licensed in several countries under specific conditions, that is, it is only to be used in immunocompetent children aged 2–7 years.