Possible European origin of the Spanish Influenza

We can note that, rather unexpectedly, the vaccination of soldiers in 1918 with a mixed bacterial vaccine reduced pneumonia and deaths in those infected with the influenza virus. This can be explained by the observation that then, and now, over half of the victims of pandemic influenza virus die because of deep-seated superinfection with respiratory bacteria.(17) Today, pneumococcus vaccines are stockpiled for use in influenza pandemics, as well as for yearly outbreaks among children and the elderly. But more research is needed with streptococcal and pneumococcal vaccines.

In modern times, the ingenuity of immunologists and molecular biologists has been applied to the design of so-called ‘universal influenza vaccines’. There is the hope of a broader-based immune response, even covering new pandemic viruses. Many of these new vaccines are composed of peptides of the influenza hemagglutinin, particularly from the stalk region, which is antigenically related between the HA subtypes (18) Other researchers have made experimental vaccines, using the internal influenza virus proteins M, NP, and polymerase PA, PB1, PB2, and also M2e (19-23). An underlying research strategy is to formulate novel vaccines to increase the magnitude of CD8 and CD4 T-cell memory to influenza proteins. Two such vaccines have reached clinical testing in the community in the European Union. (22)

We remain impressed by the care and initiative shown by our predecessors 100 years ago. Their efforts did have an impact on the level of fatalities, but, not unexpectedly, had no effect upon spread: the result, of course, of everyone’s misunderstanding of the nature of the pathogen involved. Even so, we can speculate that, had the two RAMC groups concluded that influenza was the underlying problem, in Etaples and Aldershot in 1916, they would have had better scientific grounds to embark on a two-year vaccination programme. (23)

(17) Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza. J Infect Dis. 2008;198:962–70. doi:10.1086/593027.

(18) Impagliazzo A, Milder F, Kuipers H,  Wagner MV, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. ScienceExpress. 2015; 349: 1301–06.

(19) Fiers W, De Filette M, Birkett A, Neirynck S, Min Jou W. A ‘universal’ human influenza A vaccine. Virus Res. 2004;103:173–76. doi:10.1016/j.virusres.2004.02.030

(20) Yassine HM, Boyington JC, McTamney PM,  Wei CJ, Kanekiyo M, Kong WP, Gallagher JR, Wang L, Zhang Y, Joyce MG, et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015 August;1–6

(21) Krammer F, Palese P, Steel J. Advances in universal virus vaccine design and antibody mediated therapies based on conserved regions of the hemagglutinin. Curr Top Microbiol Immunol. 2015;386:301–21. doi:10.1007/82_2014_408

(22) Ortiz JR, Hickling J, Jones R, Donabedian A, Engelhardt OG, Katz JM, Madhi SA, Neuzil KM, Rimmelzwaan GF, Southern J, et al. Report on eighth WHO meeting on developments of influenza vaccines that induce broadly protective and long-lasting immune responses: chicago, 23-24 August 2016. Vaccine. 2018;36:932–38. doi:10.1016/j.vaccine.2017.11.061.

(23) Oxford J, Gill D. Unanswered questions about the 1918 influenza pandemic: origin, pathology, and the virus itself. Lancet Infect Dis. 2018 June 20;18:e348–e354. doi:10.1016/S1473-3099(18)30359-1