Immunoglobulin Infusion as Therapy Against Influenza?

http://dx.doi.org/10.1016/j.ebiom.2017.04.021 2352-3964/© 2017 The Author(s). Published by Elsevier B With about 3–5 million severe cases and 250.000–500.000 deaths yearly, seasonal influenza infections form a constant and serious threat to the human population (Influenza (Seasonal) Fact sheet, n.d.). In addition, new influenza virus strains, often originating in birds or pigs, may cross the species barrier to humans and cause pandemics with potentially very high attack rates and sometimes high mortality (Trombetta et al., 2015). While vaccination can protect from seasonal influenza strains it will be of limited use in the first months of a pandemic since vaccine production and distribution will lag behind as experienced during the Swine Flu in 2009. Antivirals can provide an outcome and in fact have been stockpiled by several countries as a first line of defence in case of a pandemic. Yet, influenza virus appears to rapidly acquire resistance against antivirals. Thus, new intervention options are urgently needed. Intravenous immunoglobulin (IVIg) preparations consist of pooled serum IgG fractions from several thousand individuals. Originally employed as replacement therapy for immunodeficient individuals, IVIg is currently recognized as an immunomodulating intervention suitable for treatment of a variety of autoimmune, infectious and idiopathic diseases (Scheinfeld, 2016). IVIg has been used sporadically for treatment of influenza patients, mainly with the idea that the preparation will contain influenza-specific antibodies which can interfere with the infecting virus. Indeed, influenza-specific antibodies with broad specificity have been found in IVIg preparations and proved to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro (Jegaskanda et al., 2014). In this issue of EBioMedicine, Rockman and co-workers report on a study into the in vivo effects of IVIg therapy using ferrets as a wellestablished animal model for influenza (Rockman et al., 2017–in this issue). The study demonstrates that IVIg preparations from before 2009 have the capacity to ameliorate disease symptoms in ferrets infected with 2009 H1N1pdm virus, and protect from death caused by infection with lethal H5N1 virus. Thus, IVIg preparations provided protection although they did not contain antibodies elicited by the challenge viruses. This is an important observation which implies that IVIg can be used as treatment option for newly emerging virus strains. In a series of well-designed experiments the authors tried to unravel the mechanism of action of IVIg in vivo. They observed that the