2016). that come up because they are a little too controversial? In em Immune Memory space and Vaccines: Great Debates /em , Editors Rafi Ahmed and Shane Crotty have put together a collection of content articles on such questions, written by thought leaders in these fields, with the freedom to talk about the issues as they observe match. This short, HS-1371 innovative format seeks to bring a fresh perspective by motivating authors to be opinionated, focus on what is most interesting and current, and prevent restating introductory material covered in many other evaluations. The Editors posed 13 interesting questions critical for our understanding of vaccines and immune memory to a broad group of specialists in the field. In each case, several different perspectives are provided. Note that while each author knew that there were additional scientists dealing with the same query, they did not know who these authors were, which ensured the independence of the opinions and perspectives indicated in each article. Our hope is definitely that readers enjoy these content articles and that they trigger many more discussions on these important topics. Influenza computer virus infections cause significant morbidity, mortality, and economic loss worldwide every year. It is estimated that seasonal influenza viruses cause 2C5 million severe instances and 250,000 to 500,000 deaths per year globally (WHO 2016). In the United States alone, seasonal influenza computer virus infections cause approximately 24,000 deaths (CDC 2010) and an economic loss of US$87 billion per time of year (Molinari et al. 2007). In addition, influenza pandemics happen at irregular intervals and may claim millions of lives, as evidenced from the 1918 pandemic, which resulted in an estimated 50 million deaths worldwide (Palese HS-1371 2004). Current influenza computer virus vaccines are efficacious but only if they may be well matched to the circulating strains. The immunity induced by these vaccines is mainly focused on the immunodominant globular head website of the major viral glycoprotein hemagglutinin (HA). This website has a high plasticity and changes regularly, therefore escaping herd immunity (also called community safety, a type of indirect safety when HS-1371 a large proportion of a population has become immune to a pathogen) in a process called antigenic drift (Krammer and Palese 2015). Therefore, influenza computer virus vaccines have to be reformulated and readministered on an annual basis. The annual vaccine strain selection is based on surveillance, but mismatches between vaccine strains and circulating strains happen regularly, leading to the loss of vaccine effectiveness (de Jong et al. 2000; Tricco et al. 2013; Aquino et al. 2014; Flannery et al. 2015; Xie et al. 2015). Furthermore, seasonal influenza computer virus vaccines have low or no effectiveness against novel pandemic viruses, and the generation and production of matched pandemic vaccines requires at least 6 months (Krammer and Palese 2015). During this lengthy process, the population is at risk and pandemic vaccines, like HS-1371 the one in 2009 2009, often come too late to the market to make an impact (www.virology.ws/2010/12/09/pandemic-influenza-vaccine-was-too-late-in-2009). Consequently, improved influenza computer virus vaccines that induce long-lasting and broad immunity against both seasonal HS-1371 and pandemic/zoonotic influenza viruses are urgently needed. CONSERVED VIRAL TARGET ANTIGENS FOR VACCINE DEVELOPMENT Whereas the globular head website of the HA, the main target of currently licensed influenza computer virus vaccines, continuously changes, other parts of the computer virus are more conserved. These parts include the membrane-proximal stalk website of the HA (Krammer and Palese 2013), several domains of the second surface glycoprotein neuraminidase (NA) (Wohlbold and Krammer 2014), the ectodomain of the ion channel M2 (M2e) (Schotsaert et al. 2009), as well as proteins that are located inside Itgb2 the virion, including the matrix protein (M1) and the nucleoprotein (NP) (Table 1) (Give et al. 2014, 2016). Vaccines against all of these targets are.