The Future of Influenza Vaccines: A Historical and Clinical Perspective

Abstract

For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before. However, vaccines optimal against some infectious diseases, influenza among them, have remained elusive. This review will highlight the challenges that influenza viruses pose for rational vaccine design. In particular, it will consider the clinically beneficial endpoints, beyond complete sterilizing immunity, that have been achieved with vaccines against other infectious diseases, as well as the barriers to achieving similar success against influenza.

Keywords: effectiveness; efficacy; influenza; morbidity; mortality; transmission; vaccine.

Figure 1

Milestones in the history of influenza vaccines [14,15,16,17,18,19,20,21,22,23,24,25]. IIV, inactivated influenza vaccine; WHO, World Health Organization; LAIV, live attenuated influenza vaccine.

Figure 2

Influenza deaths in pandemic and epidemic influenza. Data from the pandemic year of 1918 are graphed against the left y-axis as the excess death rate above the baseline death rate observed in the non-pandemic year of 1914 [93]. Data from 2001–2009 are graphed against the right y-axis as the age-adjusted death rate (AADR), calculated as follows: Influenza-attributed crude death rate per 100,000 population (CDR) = the number of influenza deaths in each age group ÷ the population in that age group × 100,000; AADR = CDR × the proportion of the entire population within that age group. Influenza death counts by age group were obtained from published data for the U.S. [95] and England [94]. U.S. census figures from 2010 [96] and U.K. national population estimates for England (code E92000001) in mid-year 2005 [97] were used to approximate the number and age distribution of the population at risk during each time period.