Vaccine 27 (2009) 4381–4387 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Review Eleven years of Inflexal ® V—a virosomal adjuvanted influenza vaccine Christian Herzog * , Katharina Hartmann, Valérie Künzi, Oliver Kürsteiner, Robert Mischler, Hedvika Lazar 1 , Reinhard Glück Berna Biotech AG, Rehhagstrasse 79, 3018 Berne, Switzerland article info Article history: Received 16 December 2008 Received in revised form 23 April 2009 Accepted 10 May 2009 Available online 29 May 2009 Keywords: Influenza vaccine Virosomes Adjuvant Inflexal ® V abstract Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold over 41 million doses worldwide of the virosomal adjuvanted influenza vaccine, Inflexal ® V. Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal ® V have been com- pleted in which 3920 subjects participated. During its decade on the market, Inflexal ® V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and its purity is reflected in the low ovalbumin content. By mimicking natural infection, the vaccine is highly efficacious. Inflexal ® V is the only adjuvanted influenza vaccine licensed for all age groups and shows a good immunogenicity in both healthy and immunocompromised elderly, adults and children. This review presents and discusses the experience with Inflexal ® V during the past decade. © 2009 Elsevier Ltd. All rights reserved. Contents 1. Influenza viruses and epidemics ................................................................................................................... 4381 2. Impact of influenza vaccination on health economics ............................................................................................ 4382 3. Virosomes as an adjuvant system ................................................................................................................. 4382 4. Immunogenicity of Inflexal ® V .................................................................................................................... 4382 5. Safety of Inflexal ® V ................................................................................................................................ 4383 6. Clinical experience with Inflexal ® V ............................................................................................................... 4383 6.1. Children ..................................................................................................................................... 4384 6.2. Adults ....................................................................................................................................... 4385 6.3. The elderly .................................................................................................................................. 4385 7. Conclusion .......................................................................................................................................... 4385 Acknowledgement ................................................................................................................................. 4386 References ......................................................................................................................................... 4386 1. Influenza viruses and epidemics Influenza is one of the most important respiratory infections of humans, responsible for 300,000–500,000 annual deaths world- wide [1,2]. The influenza viruses are capable of genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses [3]. Antigenic drift is the grad- ual evolution of viral strains, due to frequent mutations of the surface glycoproteins hemagglutinin and neuraminidase [4,5]. Con- sequently, infecting viruses can no longer be neutralized effectively * Corresponding author. Tel.: +41 980 62 51; fax: +41 980 67 72. E-mail address: christian.herzog@crucell.ch (C. Herzog). 1 Current address: Kenta Biotech AG, Rehhagstrasse 79, 3018 Berne, Switzerland. by the antibodies raised against previously circulating strains, allowing the virus to spread rapidly among the population [6,7]. In case of antigenic shift, an influenza virus emerges to which the human population is immunologically naïve, resulting in devastat- ing pandemics [8]. Outbreaks of influenza are therefore an ongoing public health threat and require global pandemic preparedness. Recent findings from an extensive research collaboration on pre- diction of the evolution of influenza viruses suggest that seasonal influenza strains constantly evolve in overlapping epidemics in Asia before sweeping the rest of the world every year [9]. In Europe, the average length of an influenza season is 12–19 weeks, and during the last 7 years there was a west–east and south–north peak of activity [10]. Several hypotheses exist why influenza viruses tend to strike in cold weather. Recently, it was suggested that lipid order- ing in the virus envelope may contribute to virus stability at lower 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.05.029