Future Influenza Research Articles

Recombinant H7 hemagglutinin expressed in glycoengineered Pichia pastoris forms nanoparticles that protect mice from challenge with H7N9 influenza virus

Cases of H7N9 human infection caused by an avian-origin H7N9 virus emerged in eastern China in 2013, leading to the urgent requirement of developing an effective vaccine to reduce its pandemic potential. In this report, the full-length recombinant H7 protein (rH7) of A/Hangzhou/1/2013 (H7N9) virus was expressed by a glycoengineered Pichia pastoris system. The rH7 protein underwent complex glycosylation modifications and polymerized to nanoparticles of 30–50 nm in diameter. Recombinant H7 (1.9 µg) elicited a > 1:40 hemagglutination inhibition titer, and 3.75 µg rH7 protected 100% of the mice in the mice challenge model with 10-fold 50% lethal dose of the A/Shanghai/2/2013 (H7N9) rat lung-adapted strain. In conclusion, rH7 produced by the glycoengineered P. pastoris can be used for vaccination against the H7N9 virus, and provides an effective platform for the rapid production of future influenza vaccines.

Systemic and respiratory T-cells induced by seasonal H1N1 influenza protect against pandemic H2N2 in ferrets

Traditional influenza vaccines primarily induce a narrow antibody response that offers no protection against heterosubtypic infections. Murine studies have shown that T cells can protect against a broad range of influenza strains. However, ferrets are a more potent model for studying immune correlates of protection in influenza infection. We therefore set out to investigate the role of systemic and respiratory T cells in the protection against heterosubtypic influenza A infections in ferrets. H1N1-priming induced systemic and respiratory T cells that responded against pandemic H2N2 and correlated with reduced viral replication and disease. CD8-positive T cell responses in the upper and lower respiratory tract were exceptionally high. We additionally confirmed that H2N2-responsive T cells are present in healthy human blood donors. These findings underline the importance of the T cell response in influenza immunity and show that T cells are a potent target for future universal influenza vaccines.

Overrepresentation of South Asian ethnic groups among cases of influenza A(H1N1)pdm09 during the first phase of the 2009 pandemic in England.

BackgroundDuring the first wave of the influenza A(H1N1)pdm09 pandemic in England in 2009, morbidity and mortality were higher in patients of South Asian (Indian, Pakistani or Bangladeshi) ethnic minority groups.ObjectivesThis study aims to provide insights in the representation of this group among reported cases, indicating susceptibility and exposure.MethodsAll laboratory‐confirmed cases including basic demographic and limited clinical information that were reported to the FluZone surveillance system between April and October 2009 were retrieved. Missing ethnicity data were imputed using the previously developed and validated South Asian Names and Group Recognition Algorithm (SANGRA). Differences between ethnic groups were calculated using chi‐square, log‐rank and t tests and rate ratios. Geographic clustering was compared using Ripley's K functions.ResultsSANGRA identified 2447 (28%) of the total of 8748 reported cases as South Asian. South Asian cases were younger (P < .001), more often male (P = .002) and more often from deprived areas (P < .001) than cases of other ethnic groups. Time between onset of symptoms and laboratory sampling was longer in this group (P < .001), and they were less often advised antiviral treatment (P < .001), however, declined treatment less. The highest cumulative incidence was seen in the West Midlands region (32.7/10 000), London (7.0/10 000) and East of England region (5.7/10 000).ConclusionsPeople of South Asian ethnic groups were disproportionally affected by the first wave of the influenza pandemic in England in 2009. The findings presented contribute to further understanding of demographic, socioeconomic and ethnic factors of the outbreak and inform future influenza preparedness to ensure appropriate prevention and care.

Acceptability of an inactivated influenza vaccine delivered by microneedle patch: Results from a phase I clinical trial of safety, reactogenicity, and immunogenicity

ObjectiveThis study sought to evaluate the acceptability of inactivated influenza vaccine delivered by microneedle patch (MNP) in comparison to inactivated influenza vaccine (IIV) delivered by hypodermic needle.Design, Setting, and Participants.From the general population of Atlanta, Georgia, we screened 112 and enrolled 100 healthy adult subjects ages 18 to 49 years.Main Outcome(s) and Measure(s).Our participants were randomized to 4 groups of 25 per arm: (1) IIV by MNP administered by healthcare worker (HCW), (2) IIV by MNP self-administered by study participants, (3) IIV by intramuscular (IM) injection administered by HCW or (4) placebo by MNP administered by HCW. We administered four questionnaires: at Day 0 before and after study product delivery, and at Days 8 and 28. ResultsAt baseline, 98.6% of participants receiving MNP vaccination reported an overall positive experience with MNPs, compared to 86.4% for participants receiving IM vaccination. For future influenza vaccination, study participants (N = 99) preferred MNP (n = 65, 69.9%) to injections or nasal spray (n = 20, 21.5%), and the preference for MNP increased from Day 0 to Day 28. Factor analyses resulted in two scaled measures including MNP Use Perceptions (a = 0.799, n = 5 items) and MNP Perceived Convenience (a = 0.844, n = 4 items) that were included in longitudinal assessments; while findings reflect significant differences across treatment groups on mean scores for ease of use, MNP perceived protection, MNP reliability, and MNP selection knowledge, all groups reported their belief that influenza vaccination by MNP would be reliable and protective, as well as easy-to-use and convenient. Conclusions and RelevanceMost participants were accepting of IIV vaccination by MNP and preferred it to injection. Delivery of IIV by MNP may help increase vaccination coverage.

Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine.

Neuraminidase (NA) is an influenza surface protein that helps to free viruses from mucin-associated decoy receptors and to facilitate budding from infected cells. Experiments have demonstrated that anti-NA antibodies protect animals against lethal influenza challenge by numerous strains, while decreasing pulmonary viral titers, symptoms, and lung lesions. Studies in humans during the influenza A/H3N2 pandemic and in healthy volunteers challenged with influenza A/H1N1 showed that anti-NA immunity reduced symptoms, nasopharyngeal viral shedding, and infection rates. Despite the benefits of anti-NA immunity, current vaccines focus on immunity against hemagglutinin and are not standardized to NA content leading to limited and variable NA immunogenicity. Purified NA has been shown to be safe and immunogenic in humans. Supplementing current vaccines with NA may be a simple strategy to improve suboptimal effectiveness. Immunity against NA is likely to be an important component of future universal influenza vaccines.

Comparative epidemiology, phylogenetics, and transmission patterns of severe influenza A/H3N2 in Australia from 2003 to 2017.

BackgroundOver the last two decades, Australia has experienced four severe influenza seasons caused by a predominance of influenza A (A/H3N2): 2003, 2007, 2012, and 2017.MethodsWe compared the epidemiology, genetics, and transmission dynamics of severe A/H3N2 seasons in Australia from 2003 to 2017.ResultsSince 2003, the proportion of notifications in 0‐4 years old has decreased, while it has increased in the age group >80 years old (P < .001). The genetic diversity of circulating influenza A/H3N2 viruses has also increased over time with the number of single nucleotide polymorphisms significantly (P < .05) increasing. We also identified five residue positions within or near the receptor binding site of HA (144, 145, 159, 189, and 225) undergoing frequent mutations that are likely involved in significant antigenic drift and possibly severity. The Australian state of Victoria was identified as a frequent location for transmission either to or from other states and territories over the study years. The states of New South Wales and Queensland were also frequently implicated as locations of transmission to other states and territories but less so over the years. This indicates a stable but also changing dynamic of A/H3N2 circulation in Australia.ConclusionThese results have important implications for future influenza surveillance and control policy in the country. Reasons for the change in age‐specific infection and increased genetic diversity of A/H3N2 viruses in recent years should be explored.

084 T cell vaccination using conserved influenza proteins is highly protective against lethal challenge

A possible future influenza A pandemic similar to the 1918 H1N1 outbreak remains an existential public health threat. A universal influenza A vaccine that protects regardless of hemagluttinin (H) and neuraminidase (N) subgroups remains elusive. The influenza genome encodes for a few proteins highly conserved among all flu strains, including NP and M1. We sought to generate a T cell vaccine broadly protective against all influenza A viruses based on this property. Using Modified Vaccinia Ankara (MVA), we created MVA-NP and MVA-M1 vectors.

A Systematic Review Analyzing the Prevalence and Circulation of Influenza Viruses in Swine Population Worldwide.

The global anxiety and a significant threat to public health due to the current COVID-19 pandemic reiterate the need for active surveillance for the zoonotic virus diseases of pandemic potential. Influenza virus due to its wide host range and zoonotic potential poses such a significant threat to public health. Swine serve as a “mixing vessel” for influenza virus reassortment and evolution which as a result may facilitate the emergence of new strains or subtypes of zoonotic potential. In this context, the currently available scientific data hold a high significance to unravel influenza virus epidemiology and evolution. With this objective, the current systematic review summarizes the original research articles and case reports of all the four types of influenza viruses reported in swine populations worldwide. A total of 281 articles were found eligible through screening of PubMed and Google Scholar databases and hence were included in this systematic review. The highest number of research articles (n = 107) were reported from Asia, followed by Americas (n = 97), Europe (n = 55), Africa (n = 18), and Australia (n = 4). The H1N1, H1N2, H3N2, and A(H1N1)pdm09 viruses were the most common influenza A virus subtypes reported in swine in most countries across the globe, however, few strains of influenza B, C, and D viruses were also reported in certain countries. Multiple reports of the avian influenza virus strains documented in the last two decades in swine in China, the United States, Canada, South Korea, Nigeria, and Egypt provided the evidence of interspecies transmission of influenza viruses from birds to swine. Inter-species transmission of equine influenza virus H3N8 from horse to swine in China expanded the genetic diversity of swine influenza viruses. Additionally, numerous reports of the double and triple-reassortant strains which emerged due to reassortments among avian, human, and swine strains within swine further increased the genetic diversity of swine influenza viruses. These findings are alarming hence active surveillance should be in place to prevent future influenza pandemics.

100 years of influenza research seen through the lens of Covid-19.

100 years of influenza research seen through the lens of Covid-19.

Mortality burden from seasonal influenza in Chongqing, China, 2012–2018

ABSTRACT Purpose To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018. Methods We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years). Results It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5–35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3–26.0), 0.8 (95% CI: 0.7–0.8), 8.5 (95% CI: 8.1–9.0) and 5.0 (95% CI: 4.7–5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3–21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5–6.1) and 7.5 (95% CI: 6.7–8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1–168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3–7.2). Conclusions Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

Incidence and costs of hospitalized adult influenza patients in The Netherlands: a retrospective observational study.

ObjectiveInfluenza virus infections cause a high disease and economic burden during seasonal epidemics. However, there is still a need for reliable disease burden estimates to provide a more detailed picture of the impact of influenza. Therefore, the objectives of this study is to estimate the incidence of hospitalisation for influenza virus infection and associated hospitalisation costs in adult patients in the Netherlands during two consecutive influenza seasons.MethodsWe conducted a retrospective study in adult patients with a laboratory confirmed influenza virus infection in three Dutch hospitals during respiratory seasons 2014–2015 and 2015–2016. Incidence was calculated as the weekly number of hospitalised influenza patients divided by the total population in the catchment populations of the three hospitals. Arithmetic mean hospitalisation costs per patient were estimated and included costs for emergency department consultation, diagnostics, general ward and/or intensive care unit admission, isolation, antibiotic and/or antiviral treatment. These hospitalisation costs were extrapolated to national level and expressed in 2017 euros.ResultsThe study population consisted of 380 hospitalised adult influenza patients. The seasonal cumulative incidence was 3.5 cases per 10,000 persons in respiratory season 2014–2015, compared to 1.8 cases per 10,000 persons in 2015–2016. The arithmetic mean hospitalisation cost per influenza patient was €6128 (95% CI €4934–€7737) per patient in 2014–2015 and €8280 (95% CI €6254–€10,665) in 2015–2016, potentially reaching total hospitalisation costs of €28 million in 2014–2015 and €20 million in 2015–2016.ConclusionsInfluenza virus infections lead to 1.8–3.5 hospitalised patients per 10,000 persons, with mean hospitalisation costs of €6100–€8300 per adult patient, resulting in 20–28 million euros annually in The Netherlands. The highest arithmetic mean hospitalisation costs per patient were found in the 45–64 year age group. These influenza burden estimates could be used for future influenza cost-effectiveness and impact studies.Electronic supplementary materialThe online version of this article (10.1007/s10198-020-01172-1) contains supplementary material, which is available to authorized users.

The Hong Kong Influenza Virus: Treats to the Portrait after 50 Years and the Future Influenza Pandemic

Relevance . Of the different subtypes, H3N2 influenza virus subtype has the highest variability and pathogenicity, often dominates in epidemiological seasons and induces high mortality exceeding its rate in pandemic. Aim is to identify some features of H3N2 molecular characteristics which could determine its high variability and domination over other subtypes in epidemiological seasons and discuss possible nature of the future influenza pandemic. Materials and method . For the computer analysis, the database of the hemagglutinin (HA) and nucleoprotein primary structures of the H3N2, H1N1, В \Yamagata and В \Victoria strains isolated in the influenza epidemiological seasons 2009-2019 were used from the Internet. From the primary structure of their genes it were defined their translational codes. To trace the H3N2 subtype evolution in the last decade we compared the H3 dominant sequences of adjacent seasons to establish their changes. Results. It has been indicated that H3, in comparison with H1 and В \Yamagata and В \Victoria hema g glutinins, contains more cysteine and the H3N2 strain very similar to the Hong Kong influenza virus continues to circulate in birds.The H3 gene translation code contains the least number of prohibitions. During last decade the H3 dominant sequence evolves faster than H1 one. The nucleoprotein of H3N2 strains is characterized by more content of lysine and less content of arginine. Conclusion : H3N2, H1N1, В \Yamagata and В \Victoria strains one may conclude that least of all the nature restricts H3N2 to evolve and adapt to new hosts. It is likely that the following influenza pandemic will be generated by H1N1 subtype but H3N2 one and also be more mild than the 2019 pandemic.

Enhancing response preparedness to influenza epidemics: Agent-based study of 2050 influenza season in Switzerland

Incidences of seasonal influenza are increasing in severity with significant impacts on human health and on economy, due to missed working hours. As transmission of influenza is highest in spaces where persons are in close proximity, public transport networks are increasingly vulnerable in strategies to manage potential influenza epidemics. In this work, we integrate into an agent-based framework, a stochastic model that simulates, on a sub-hourly timescale, the different daily activities of all individuals in a population. Thus, the contact patterns of individuals are accurately modeled, and with the use of agent-based epidemic and mobility models, individual-level transmission of influenza, and its subsequent spread, are accurately modeled. We demonstrate this novel approach in an assessment of seasonal influenza in Switzerland for the year 2050, when Switzerland's population will exceed 11 million. In the absence of interventions, we show that, although of shorter duration, future influenza epidemics will be significantly more severe and infect more of the population. The incidence of influenza is larger during leisure and needs activities, rather than at home, school or work. We demonstrate also that influenza-transmission preventive measures are effective: the intensity of the epidemic and the total number of infections are reduced; however, there is little impact of different preventive measures on the duration of the epidemic. This work demonstrates therefore an accurate tool that can predict the spatiotemporal characteristics of an influenza epidemic, and that can be used to assess the most effective measures to mitigate the epidemic.

Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations.

Administering inactivated influenza vaccine (IIV), 13-valent pneumococcal conjugate vaccine (PCV13), and diphtheria-tetanus-acellular pertussis (DTaP) vaccine together has been associated with increased risk for febrile seizure after vaccination. We assessed the effect of administering IIV at a separate visit from PCV13 and DTaP on postvaccination fever. In 2017-2018, children aged 12 to 16 months were randomly assigned to receive study vaccines simultaneously or sequentially. They had 2 study visits 2 weeks apart; nonstudy vaccines were permitted at visit 1. The simultaneous group received PCV13, DTaP, and quadrivalent IIV (IIV4) at visit 1 and no vaccines at visit 2. The sequential group received PCV13 and DTaP at visit 1 and IIV4 at visit 2. Participants were monitored for fever (≥38°C) and antipyretic use during the 8 days after visits. There were 110 children randomly assigned to the simultaneous group and 111 children to the sequential group; 90% received ≥1 nonstudy vaccine at visit 1. Similar proportions of children experienced fever on days 1 to 2 after visits 1 and 2 combined (simultaneous [8.1%] versus sequential [9.3%]; adjusted relative risk = 0.87 [95% confidence interval 0.36-2.10]). During days 1 to 2 after visit 1, more children in the simultaneous group received antipyretics (37.4% vs 22.4%; P = .020). In our study, delaying IIV4 administration by 2 weeks in children receiving DTaP and PCV13 did not reduce fever occurrence after vaccination. Reevaluating this strategy to prevent fever using an IIV4 with a different composition in a future influenza season may be considered.

Detection of Variants With Reduced Baloxavir Marboxil Susceptibility After Treatment of Children With Influenza A During the 2018–2019 Influenza Season

During the 2018-2019 influenza seasons, we detected reduced baloxavir marboxil (baloxavir) susceptible variants with I38S or I38T amino acid substitutions on the PA subunit of influenza virus ribonucleic acid polymerase in 7 of 18 baloxavi-treated children and found that virus titer rebounded in some of these children with variants. We also found fever durations to be similar between patients with or without the variants, but the patients with variants shed the virus 3 days longer and took longer to improve clinical symptoms than those without variants. The emergence of these variants should be monitored during future influenza seasons.

Genetic characterization of influenza A(H3N2) viruses circulating in coastal Kenya, 2009-2017.

BackgroundInfluenza viruses evolve rapidly and undergo immune driven selection, especially in the hemagglutinin (HA) protein. We report amino acid changes affecting antigenic epitopes and receptor‐binding sites of A(H3N2) viruses circulating in Kilifi, Kenya, from 2009 to 2017.MethodsNext‐generation sequencing (NGS) was used to generate A(H3N2) virus genomic data from influenza‐positive specimens collected from hospital admissions and health facility outpatients presenting with acute respiratory illness to health facilities within the Kilifi Health and Demographic Surveillance System. Full‐length HA sequences were utilized to characterize A(H3N2) virus genetic and antigenic changes.ResultsFrom 186 (90 inpatient and 96 outpatient) influenza A virus‐positive specimens processed, 101 A(H3N2) virus whole genomes were obtained. Among viruses identified in inpatient specimens from 2009 to 2015, divergence of circulating A(H3N2) viruses from the vaccine strains A/Perth/16/2009, A/Texas/50/2012, and A/Switzerland/9715293/2013 formed 6 genetic clades (A/Victoria/208/2009‐like, 3B, 3C, 3C.2a, 4, and 7). Among viruses identified in outpatient specimens from 2015 to 2017, divergence of circulating A(H3N2) viruses from vaccine strain A/Hong Kong/4801/2014 formed clade 3C.2a, subclades 3C.2a2 and 3C.2a3, and subgroup 3C.2a1b. Several amino acid substitutions were associated with the continued genetic evolution of A(H3N2) strains in circulation.ConclusionsOur results suggest continuing evolution of currently circulating A(H3N2) viruses in Kilifi, coastal Kenya and suggest the need for continuous genetic and antigenic viral surveillance of circulating seasonal influenza viruses with broad geographic representation to facilitate prompt and efficient selection of influenza strains for inclusion in future influenza vaccines.

Emergency Medical Services Personnel’s Pandemic Influenza Training Received and Willingness to Work during a Future Pandemic

Objective: Identify determinants of emergency medical service (EMS) personnel’s willingness to work during an influenza pandemic. Background: Little is known about the willingness of EMS personnel to work during a future influenza pandemic or the extent to which they are receiving pandemic training. Methods: EMS personnel were surveyed in July 2018 – Feb 2019 using a cross-sectional approach; the survey was available both electronically and on paper. Participants were provided a pandemic scenario and asked about their willingness to respond if requested or required; additional questions assessed their attitudes and beliefs and training received. Chi-square tests assessed differences in attitude/belief questions by willingness to work. Logistic regressions were used to identify significant predictors of response willingness when requested or required, controlling for gender and race. Results: 433 individuals completed the survey (response rate = 82.9%). A quarter (26.8%, n = 116) received no pandemic training; 14.3% (n = 62) participated in a pandemic exercise. Significantly more EMS personnel were willing to work when required versus when only requested (88.2% vs 76.9%, X2 = 164.1, p < .001). Predictors of willingness to work when requested included believing it is their responsibility to work, believing their coworkers were likely to work, receiving prophylaxis for themselves and their family members, and feeling safe working during a pandemic. Discussion: Many emergency medical services personnel report lacking training or disaster exercises related to influenza pandemics, and a fair percentage are unwilling to work during a future event. This may limit healthcare surge capacity and could contribute to increased morbidity and mortality. Findings from this study indicate that prehospital staff’s attitudes and beliefs about pandemics influence their willingness to work. Pre-event training and planning should address these concerns.

Influenza Vaccination, Self-reported Illness, and Obstacles for Vaccination Among the 2010 ROTC Warrior Forge Cadet Cohort.

This study evaluates a large cohort of college students after the 2009-2010 pandemic H1N1 influenza season. The objective was to assess influenza vaccination status, influenzalike illnesses (ILIs), and other characteristics associated with attaining immunizations. This study was conducted during the summer 2010 the Reserve Officer Training Corps Leadership Development and Assessment Course involving 6272 college students. A voluntary, anonymous questionnaire was administered to assess study objectives. Vaccination rates were 39.9% for pandemic H1N1, 40.6% for seasonal influenza, and 32.6% for receiving both vaccinations. Age less than 25 and having a Reserve Officer Training Corps scholarship were associated with lower odds of receiving vaccinations, whereas entering the nursing field and simultaneous membership in the Army reserve forces were associated with higher odds of vaccination. There are 11.2% of respondents reported having an ILI, including 4.3% with severe ILI. There were 4184 reasons indicated for not attaining influenza vaccinations, which are listed in categorical groupings. A historical anchor for vaccination rates and ILI is provided in a large cohort of college students following the 2009 H1N1 influenza pandemic. Influenza immunization locations were determined, as was self-reported obstacles to receiving vaccinations. These are important results for public health leaders seeking to increase vaccination rates during future influenza seasons.

Epidemiological features and time-series analysis of influenza incidence in urban and rural areas of Shenyang, China, 2010-2018.

In recent years, there have been a significant influenza activity and emerging influenza strains in China, resulting in an increasing number of influenza virus infections and leading to public health concerns. The aims of this study were to identify the epidemiological and aetiological characteristics of influenza and establish seasonal autoregressive integrated moving average (SARIMA) models for forecasting the percentage of visits for influenza-like illness (ILI%) in urban and rural areas of Shenyang. Influenza surveillance data were obtained for ILI cases and influenza virus positivity from 18 sentinel hospitals. The SARIMA models were constructed to predict ILI% for January-December 2019. During 2010-2018, the influenza activity was higher in urban than in rural areas. The age distribution of ILI cases showed the highest rate in young children aged 0-4 years. Seasonal A/H3N2, influenza B virus and pandemic A/H1N1 continuously co-circulated in winter and spring seasons. In addition, the SARIMA (0, 1, 0) (0, 1, 2)12 model for the urban area and the SARIMA (1, 1, 1) (1, 1, 0)12 model for the rural area were appropriate for predicting influenza incidence. Our findings suggested that there were regional and seasonal distinctions of ILI activity in Shenyang. A co-epidemic pattern of influenza strains was evident in terms of seasonal influenza activity. Young children were more susceptible to influenza virus infection than adults. These results provide a reference for future influenza prevention and control strategies in the study area.

Hemagglutinin Inhibitors are Potential Future Anti-Influenza Drugs for Mono- and Combination Therapies.

Infections by H1-H16 influenza A viruses require sufficient binding of viral hemagglutinins (HAs) to specific target receptors, glycoconjugates bearing sialyl sugar chains, on the host cell surface. Synthesized sialyl sugar chains targeting sialyl sugar-binding sites in HAs that are immutable as long as the virus does not switch to a different host species might therefore be highly effective candidate drugs for inhibition of the initial required step of virus entry. In this chapter, we describe the following aspects of updated sialyl sugar chains as influenza A virus HA inhibitors (HAIs): (1) mode of terminal sialyl-galactose linkage, (2) molecular length and structure of sialyl glycan receptors, (3) multivalent sialyl sugar chain dimension, (4) clustering of sialyl sugar chains on macromolecular scaffolds, and (5) enhancement of the stability of sialyl sugar chain HA inhibitors. We also discuss about the use of HAI-based combinations that should be considered for future influenza therapy.