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Background. Serum antibody to the hemagglutinin (HA) of influenza viruses is a correlate and predictor of immunity to influenza in humans; the relative values of other correlates are uncertain. Methods. Serum and nasal secretions (NS) were collected in fall and spring of 2009—2011 from healthy adults who were monitored for acute respiratory illness (ARI). Serum samples were tested for hemagglutination-inhibition (HAI) antibody increase and secretions for virus if ill; enrollment sera were also tested for neuraminidase-inhibiting (NI) antibody and NS for neutralizing (neut), NI, immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-HA antibody. Results. Serum anti-HA and anti-neuraminidase (NA) antibody titers to 2009(H1N1) pandemic influenza virus (pH1N1) correlated with titers in NS (including IgA and IgG antibody). Increasing anti-HA and anti-NA titers in serum and NS tests all correlated with reducing infection and infection-associated illness. Multivariate analyses indicated serum HAI and NI each independently predicted immunity to infection and infection-associated illness. Only serum NI independently predicted reduced illness among infected subjects. Conclusions. Increasing anti-HA and NA antibody in serum and secretions correlated with reducing pH1N1 influenza virus infection and illness in healthy young adults. Both anti-HA and anti-NA antibody are independent predictors of immunity to influenza; ensuring induction of both by vaccination is desirable.

To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.

► Minimal reactogenicity for 5 inactivated vaccines and a live vaccine. ► Similar serum anti-hemagglutinin antibody responses to 5 inactivated vaccines. ► All 5 inactivated vaccines induced serum anti-neuraminidase antibody. Serum antibody to the hemagglutinin (HA) surface protein of influenza virus induced by influenza vaccination is a correlate of protection against influenza. The neuraminidase (NA) protein is also on the surface of the virus; antibody to it has been shown to impair virus release from infected cells and to reduce the intensity of influenza infections in animal models and in humans challenged with infectious virus. Recently we have shown that NA inhibiting antibody can independently contribute to immunity to naturally-occurring influenza immunity in the presence of antibody to the HA. The present study was conducted to evaluate induction of antibody to the NA and the HA by commercially available influenza vaccines. Healthy young adults were vaccinated with one of five commercially available trivalent inactivated vaccines or live influenza vaccine. Frequencies of serum antibody and fold geometric mean titer (GMT) increases four weeks later were measured to each of the three vaccine viruses (A/H1N1, A/H3N2, B) in hemagglutination-inhibition (HAI) and neutralization (neut) assays. Frequency and fold GMT increase in neuraminidase-inhibition (NI) antibody titers were measured to the influenza A viruses (A/H1N1, A/H3N2). No significant reactogenicity occurred among the vaccinated subjects. The Fluvirin inactivated vaccine induced more anti-HA antibody responses and a higher fold GMT increase than the other inactivated vaccines but there were no major differences in response frequencies or fold GMT increase among the inactivated vaccines. Both the frequency of antibody increase and fold GMT increase were significantly lower for live vaccine than for any inactivated vaccine in HAI and neut assays for all three vaccine viruses. Afluria inactivated vaccine induced more N1 antibody and Fluarix induced more N2 antibody than the other vaccines but all inactivated vaccines induced serum NI antibody. The live vaccine failed to elicit any NI responses for the N2 NA of A/H3N2 virus and frequencies were low for the N1 of A/H1N1 virus. Trivalent inactivated influenza vaccines with similar HA dosage induce similar serum anti-HA antibody responses in healthy adults. Current inactivated vaccines all induce serum anti-NA antibody to the N1 and N2 NA proteins but some are better than others for N1 or N2. The live vaccine, Flumist, was a poor inducer of either anti-HA or anti-NA serum antibody compared to inactivated vaccine in the healthy adults. In view of the capacity for contributing to immunity to influenza in humans, developing guidelines for NA content and induction of NA antibody is desirable.

Identification of the host genetic factors that contribute to variation in vaccine responsiveness may uncover important mechanisms affecting vaccine efficacy. We carried out an integrative, longitudinal study combining genetic, transcriptional, and immunologic data in humans given seasonal influenza vaccine. We identified 20 genes exhibiting a transcriptional response to vaccination, significant genotype effects on gene expression, and correlation between the transcriptional and antibody responses. The results show that variation at the level of genes involved in membrane trafficking and antigen processing significantly influences the human response to influenza vaccination. More broadly, we demonstrate that an integrative study design is an efficient alternative to existing methods for the identification of genes involved in complex traits. Vaccines increase resistance to disease by priming the immune system to respond to specific viruses or microorganisms. By presenting a weakened (or dead) form of a pathogen, or its toxins or surface proteins, to the immune system, vaccines trigger the production of antibodies against the virus or microorganism. If a vaccinated individual then encounters the pathogen, their immune system should be able to recognize and destroy it. Many vaccines also include a secondary agent, known as an adjuvant, to further stimulate the immune response. Influenza, an RNA virus commonly referred to as the ‘flu’, is an infectious disease that affects both birds and mammals. Seasonal epidemics occur each year affecting 2–7% of the population. According to the World Health Organization, influenza leads to nearly 5 million hospitalizations each year and causes up to half a million deaths. Vaccination is a primary strategy for the prevention of seasonal influenza, but responses to the vaccine vary markedly, partly because of variation in the genetic makeup or genotype of individuals. However, the details of how genes influence response to vaccination, and indeed susceptibility to influenza, remain unclear. To investigate the genetic basis of variation in the immune response of healthy adults to the seasonal influenza vaccine, Franco et al. combined information about the genotypes of individuals with measurements of their gene transcription and antibody response to vaccination. They identified 20 genes that contributed to differential immune responses to the vaccine. Almost half of these encode proteins that are not specifically associated with the immune system, but have more general roles in processes such as membrane trafficking and intracellular transport. Focusing on these genes may enable researchers to spot those individuals who are less likely to respond to a vaccine. It could also open up new avenues of research for vaccine development: rather than designing adjuvants that target known immune mechanisms, researchers should develop adjuvants that target the proteins encoded by these 20 genes.

Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918–1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this century's three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968–1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957–1958 influenza A (H2N2) and the 1918–1919 influenza A (H1N1) pandemics occurred among persons < 65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons < 65 years old should be considered in planning for pandemics.

To identify an adjuvant that enhances antibody responses in respiratory secretions to inactivated influenza virus vaccine (IVV), a comparison was made of responses to intranasal vaccinations of mice with IVV containing monophosphoryl lipid A (MPL), type I interferon (IFN) or cholera toxin B (CTB). Antibody in nasal secretions and lung wash fluids from mice was increased after vaccination and lung virus was significantly reduced after challenge to a similar level in each adjuvant group. Interferon was selected for a trial in humans. Trivalent inactivated influenza vaccine was given intranasally to healthy adult volunteers alone or with 1 million units (Mu) or 10 Mu of alpha interferon. Vaccinations were well tolerated but neither serum hemagglutination-inhibiting nor neutralizing antibody responses among the vaccine groups were significantly different. Similarly, neither neutralizing nor IgA antibody responses in nasal secretions were significantly different. Thus, despite exhibiting a significant adjuvant effect in mice, interferon did not exhibit an adjuvant effect for induction of antibody in respiratory secretions of humans to inactivated influenza virus vaccine given intranasally.

The first anthology devoted to the theory and practice of all forms of public philosophy A Companion to Public Philosophy brings together in a single volume the diverse practices, modalities, and perspectives of this rapidly growing field. Forty-two chapters written by established practitioners and newer voices alike consider questions ranging from the definition of public philosophy to the value of public philosophy to both society and philosophy itself. Throughout the book, philosophers offer insights into the different publics they have engaged, the topics they have explored, the methods they have used and the lessons they have learned from these engagements. The Companion explores important philosophical issues concerning the practice of philosophy in the public sphere, how public philosophy relates to advocacy, philosophical collaborations with political activists, locations where public philosophy can be done, and more. Many essays highlight underserved topics such as effective altruism, fat activism, trans activism, indigenous traditions, and Africana philosophy, while other essays set the stage for rigorous debates about the boundaries of public philosophy and its value as a legitimate way to do philosophy. * Discusses the range of approaches that professional philosophers can use to engage with non-academic audiences * Explores the history and impact of public philosophy from the time of Socrates to the modern era * Highlights the work of public philosophers concerning issues of equity, social justice, environmentalism, and medical ethics * Covers the modalities used by contemporary public philosophers, including film and television, podcasting, internet memes, and community-engaged teaching * Includes essays by those who bring philosophy to corporations, government policy, consulting, American prisons, and activist groups across the political spectrum A Companion to Public Philosophy is essential reading for philosophers from all walks of life who are invested in and curious about the ways that philosophy can impact the public and how the public can impact philosophy. It is also an excellent text for undergraduate and graduate courses on the theory and practice of public philosophy as well as broader courses on philosophy, normative ethics, and comparative and world philosophy.

Feminist Philosophies A-Z covers contemporary material in a number of feminist approaches. It illustrates the complexity, range and interconnectedness of issues in feminist philosophy while making clear the relationship of feminist philosophy to the rest of philosophy as a discipline (epistemology, metaphysics, ethics, social philosophy and metaphysics). Entries are pithy, detailed, informative and are cross-referenced to guide the reader through the lively debates in feminism.

Background. Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed. Methods. We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination. Results. Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature—including STATI, CD74, and E2F2— which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes. Conclusions. The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness.