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In order to solve the problem under the exterior wall of a building, the author proposes a thermodynamic model for HVAC. Scientific and technological progress has promoted social development, under the new development situation, people have higher requirements for living environment. In architectural design, residential environment design is the key content, especially the design of indoor temperature control system. With the continuous promotion of the national sustainable development strategy, the current architectural design pays more at?tention the green design concept, and the HVAC design is the key design content in realizing the green architectural design. In order to make HVAC design more scientific and reasonable, the author studied the concept that HVAC design needs to follow from the perspective of green buildings, and analyzed the specific ap?plication methods of HVAC design technology. The experimental results indicate that the building envelope parameters have a great impact on the building thermodynamic performance, and the annual cooling and heating loads of buildings should be comprehensively considered, reasonably determine the building envelope parameters. The building load has a low support value, so only low quality energy can meet the building load demand, when selecting the HVAC system, consider the matching of energy quality, try to introduce low grade energy, and improve energy utilization efficiency.

Olanzapine (OLZ) is one of the most effective antipsychotic agents, however, its clinical utility has been limited by weight gain. Samidorphan (SAM) is a μ-opioid receptor antagonist and it can reduce the weight gain associated with OLZ. A combination of OLZ and SAM (OLZ/SAM) has been developed to provide the antipsychotic efficacy of OLZ, while mitigating OLZ-associated weight gain.A comprehensive literature search was conducted in PubMed. Key search terms included SAM and weight gain associated with OLZ. The pharmacological action, clinical efficacy, and safety of SAM were reviewed.OLZ can lead to weight gain. SAM is a new drug that acts as an opioid receptor antagonist that can decrease weight gain. SAM mitigates OLZ-associated weight gain while preserving the antipsychotic efficacy of OLZ. Clinical trials have confirmed that OLZ/SAM significantly improved psychotic symptoms, and resulted in significantly less weight gain than OLZ. OLZ/SAM was well tolerated. Therefore, it is a potential new treatment option for schizophrenia.

Affected by the deep cut slope at the plateau edge, the groundwater in most areas is deeply buried, and the runoff is concentrated. Without any barrier, the karst groundwater is finally discharged to the valley. Therefore, the direction of drilling wells in the plateau slope area is toward finding local favorable water rich blocks, which are relative groundwater accumulation areas under the control of structure, lithology, and landform. These areas often have obvious geological boundary conditions (such as the presence of a water resisting layer in the vertical direction, the development of a fault fracture zone in the plane), and their corresponding physical boundary often has a relatively low or high resistance to the surrounding rock. In this paper, the comprehensive geophysical method is used to study the application of water prospecting in the plateau slope of Shuangnuo village, Fuyuan, Yunnan Province. First, according to the hydrogeological conditions (the development of a fault fracture zone and clastic rock is unknown), the plane distribution range and vertical development of the low-resistivity abnormal fault fracture zone are determined using the electrical resistance romography (less than 100 m) and audio magnetotelluric methods (100–500 m). Vertically, the development depth and thickness of the clastic rock aquifuge (P 1 l) are determined using the audio frequency magnetotelluric method, which provides a basis for the maximum depth of the borehole layout. The combination of the electrical resistance romography and audio frequency magnetotelluric methods can delineate the favorable water rich block in the study area well and verify that the study area has the prerequisite to become a water prospecting target. Then, the composite profiling, microtremor horizontal-to-vertical spectral ratio (HVSR), apparent resistivity sounding, and K reflection coefficient methods are carried out in the favorable water rich block delineated by the electrical resistance romography and audio frequency magnetotelluric methods to finally determine the best location of the borehole layout. The optimal borehole layout location (positioning) is determined through the synchronous low resistivity anomaly of the composite profiling method, and the synchronous low resistivity anomaly is determined as a karst fracture zone (qualitative determination) in combination with the HVSR high-value anomaly of the microtremor method. The development depth (depth determination) of the karst fracture zone is finally determined by using the apparent resistivity sounding and K curves. According to the above research, the depth of the drilled hole is 243.5 m, and the water inflow is 144.3 m 3 / day, successfully solving the serious water shortage problem in the local area. The case study results show that the combination of geophysical prospecting methods, namely, the electrical resistance romography, audio frequency magnetotelluric, composite profiling, microtremor, apparent resistivity sounding, and k-reflection coefficient methods, is effective for water exploration in the plateau slope zone.

Before the transaction data in the blockchain is successfully linked, its signature must be publicly verified by a large number of nodes in the blockchain, which is also one of the ways to leak transaction information. To alleviate the contradiction between the public verifiability of signatures and the protection of transaction privacy, we introduce a verifiably encrypted signature scheme into the blockchain. A verifiably encrypted signature scheme contains two parts of signature information: the encrypted signature is used for public verification, and the ordinary signature is used for internal verification. To reach this goal even better, we design a new lattice-based verifiably encrypted signature scheme, which separates the parameter settings of the signer and the adjudicator, and replaces the Gaussian sampling algorithm with a small range of uniform random sampling, achieving better efficiency and security.

Introduction: Surufatinib (also known as HMPL-012, sulfatinib) is a novel oral tyrosine kinase inhibitor (TKI), which has the dual activity of anti-angiogenesis and immune regulation. In December 2...

Background Although ferret antisera used in influenza surveillance did not detect antigenic drift of A(H1N1)pdm09 viruses during the 2015-2016 season, low vaccine effectiveness was reported in adults. We investigated the immune basis of low responses to circulating A(H1N1)pdm09 viruses after vaccination. Methods Prevaccination and postvaccination serum samples collected from >300 adults (aged 18-49 years) in 6 seasons (2010-2011 to 2015-2016) were analyzed using hemagglutination inhibition assays to evaluate the antibody responses to 13 A(H1N1) viruses circulated from 1977 to 2016. Microneutralization and serum adsorption assays were used to verify the 163K and 223R specificity of antibodies. Results Individual antibody profiles to A(H1N1) viruses revealed 3 priming patterns: USSR/77, TW/86, or NC/99 priming. More than 20% of adults had reduced titers to cell-propagated circulating 6B.1 and 6B.2 A(H1N1)pdm09 viruses compared with the A/California/07/2009 vaccine virus X-179A. Significantly reduced antibody reactivity to circulating viruses bearing K163Q was observed only in the USSR/77-primed cohort, whereas significantly lower reactivity caused by egg-adapted Q223R change was detected across all 3 cohorts. Conclusion Both 163K specificity driven by immune priming and 223R specificity from egg-adapted changes in the vaccine contributed to low responses to circulating A(H1N1)pdm09 viruses after vaccination. Our study highlights the need to incorporate human serology in influenza surveillance and vaccine strain selection.

An aggregate signature turns multi-message multi-authentication into multi-message single-authentication, reducing the required storage space, transmission cost, and number of verification calculations, and is suitable for fast message authentication in the big data era, particularly in wireless sensor networks and secure email systems. Many aggregate signature schemes have been proposed, including lattice-based ones, which have good resistance to quantum machine attacks. However, the existing lattice-based aggregate signature schemes, which either have strict requirements on the signing order or encounter security risks, are not suitable for the unordered polymerization environment. In this paper, we accordingly propose a lattice-based unordered aggregate signature scheme. The proposed scheme makes use of the intersection method and solves the unordered aggregate problem of lattice signatures with different public keys. Therefore, it avoids both the signing order limitation and the risk of single signature forgery. Furthermore, the scheme follows the improved security model; hence, it is robust against collusion attacks. In addition, the scheme's security depends on the small integer solution problem, which enables the scheme to resist quantum algorithm attacks.

Background Recent outbreaks of swine-origin influenza A(H3N2) variant (H3N2v) viruses have raised public health concerns. Previous studies indicated that older children and young adults had the highest levels of hemagglutination-inhibition (HI) antibodies to 2010-2011 H3N2v viruses. However, newly emerging 2013 H3N2v have acquired antigenic mutations in the hemagglutinin at amino acid position 145 (N145K/R). We estimated the levels of serologic cross-reactivity among humans primed with seasonal influenza A(H3N2) (sH3N2), using postinfection ferret antisera. We also explored age-related HI antibody responses to 2012-2013 H3N2v viruses. Methods Human and ferret antisera were tested in HI assays against 1 representative 2012 H3N2v (145N) and 2 2013 H3N2v (145K/R) viruses, together with 9 sH3N2 viruses circulating since 1968. Results Low levels of cross-reactivity between the H3N2v and sH3N2 viruses from the 1970s-1990s were observed using postinfection ferret antisera. The overall seroprevalence among the sH3N2-primed population against 2012-2013 H3N2v viruses was >50%, and age-related seroprevalence was observed. Seroprevalence was significantly higher to 2013 H3N2v than to 2012 H3N2v viruses among some children likely to have been primed with A/Sydney/5/97-like (145K) or A/Wuhan/359/95-like viruses (145K). Conclusions A single substitution (N145K/R) was sufficient to affect seropositivity to H3N2v viruses in some individuals. Insight into age-related antibody responses to newly emerging H3N2v viruses is critical for risk assessment and pandemic preparedness.

Digital signature with proxy delegation, which is a secure ownership enforcement tool, allows an original signer to delegate signature rights to a third party called proxy, so that the proxy can sign messages on behalf of the original signer. Many real-world applications make use of this secure mechanism, e.g., digital property transfer. A traditional digital signature mechanism is required to bind a message and its signature together for verification. This may yield extra cost in bandwidth while the sizes of message and signature are relatively huge. Message recovery signature, enabling to reduce the cost of bandwidth, embeds a message into the corresponding signature; therefore, only the signature will be transmitted to the verifier and the message can further be recovered from the signature. In this paper, we, for the first time, propose a novel digital signature scheme in the identity-based context with proxy delegation and message recovery features and, more importantly, our scheme is quantum resistant, in a particular lattice-based signature. Our scheme achieves delegation information and signature existential unforgeability against adaptive chosen warrant and identity. Compared with the seminal lattice-based message recovery signature, our scheme is independent from public key infrastructure, realizes delegation transfer of signature rights, and compresses signature length ulteriorly. To the best of our knowledge, this paper is the first of its type.

The internet-of-things (also known as IoT) connects a large number of information-sensing devices to the Internet to collect all kinds of information needed in real time. The reliability of the source of a large number of accessed information tests the processing speed of signatures. Batch signature allows a signer to sign a group of messages at one time, and signatures’ verification can be completed individually and independently. Therefore, batch signature is suitable for data integration authentication in IoT. An outstanding advantage of batch signature is that a signer is able to sign as many messages as possible at one time without worrying about the size of signed messages. To reduce complexity yielded by multiple message signing, a binary tree is usually leveraged in the construction of batch signature. However, this structure requires a batch residue, making the size of a batch signature (for a group of messages) even longer than the sum of single signatures. In this paper, we make use of the intersection method from lattice to propose a novel generic method for batch signature. We further combine our method with hash-and-sign paradigm and Fiat–Shamir transformation to propose new batch signature schemes. In our constructions, a batch signature does not need a batch residue, so that the size of the signature is relatively smaller. Our schemes are securely proved to be existential unforgeability against adaptive chosen message attacks under the small integer solution problem, which shows great potential resisting quantum computer attacks.

Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome–DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of≥40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines.

The aim of the present study was to obtain a marine bacterium active against Karenia mikimotoi from the East China Sea and to characterize its extracellular algicidal substances. Using preparative high-performance liquid chromatography (prep-HPLC) and electrospray ionization/quadrupole-time of flight mass spectrometer coupled with a high-performance liquid chromatography (LC/MS-Q-TOF) system, we purified the alga-lysing substance produced by strain ZR-2 and determined its molecular structure. Based on morphology and l6S ribosomal DNA (rDNA) sequence analysis, the ZR-2 strain was highly homologous to Thalassospira species. Algicidal activity against K. mikimotoi was detected in the cell-free filtrate but not in bacterial cells. The alga-lysing substance produced by ZR-2 was ethanol-soluble and thermostable, with a retention time of 6.3 min and a measured elemental composition of C7H5O2 ([M-H](-) ion at m/z 121.0295). The alga-lysing substance produced by ZR-2 was determined to be benzoic acid. Compared with the negative control, both purified ZR-2 bacteria-free filtrate and standard benzoic acid promoted K. mikimotoi cell disruption and induced K. mikimotoi cell content leakage. Our study is the first to report benzoic acid activity against K. mikimotoi as well as production of benzoic acid by a Thalassospira species.

The role of pre-existing immunity for influenza vaccine responses is of great importance for public health, and thus has been studied in various contexts, yet the impact of differential priming on vaccine responses in the midst of antigenic drift remains to be elucidated. To address this with antigenically related viruses, mice were first primed by either infection or immunization with A/Puerto Rico/8/34 (PR8) virus, then immunized with whole-inactivated A/Fort Monmouth/1/47 (FM1) virus. The ensuing vaccine responses and the protective efficacy of FM1 were superior in PR8 infection-primed mice compared to PR8 immunization-primed or unprimed mice. Increased FM1-specific Ab responses of PR8 infection-primed mice also broadened cross-reactivity against contemporary as well as antigenically more drifted strains. Further, prior infection heightened the protective efficacy of antigenically distant strains, such as A/Brisbane/59/2006 infection followed by immunization with split pandemic H1N1 vaccine (A/California/07/2009). Therefore, influenza infection is a significant priming event that intensifies future vaccine responses against drift strains.

Carbon dots (C-dots) are a kind of fluorescent nanoparticles that are strongly fluorescent, non-blinking, and can be easily synthesized at low cost. Their emission color can be tuned by varying the excitation wavelength. Their properties make them strong competitors to semiconductor quantum dots. Synthetic approaches for C-dots can be classified into two categories, viz. top-down and bottom-up methods. Surface passivated and functionalized C-dots can be utilized to sense pH values, metal ions and organic molecules. Owing to their low cytotoxicity, biocompatibility and impressive photostability, long-term observations become possible. C-dots also show promise as labels and for bioimaging. This review (with 142 refs.) is divided into several sections. The first covers commonly used methods for preparation of C-dots including laser ablation, arc discharge, electrochemical methods, pyrolytic processes, template based methods, microwave assisted methods, chemical oxidation methods, reverse micelle based methods, etc. The first section also covers methods for surface functionalization and passivation. We continue by discussing the spectroscopic properties and other physical and chemical properties of C-dots (fluorescence, up-conversion fluorescence, methods for enhancing photoluminescence, effects of pH value, cytotoxicity, etc.). Another section covers the characterization including TEM and XRD. Applications in biology are summarized and subdivided into in vitro imaging, in vivo imaging, chemical probe, quantitation of biomacromolecules, but also in drug delivery, photoacoustic imaging and anticancer therapy. We finally discuss current challenges and perspectives in this promising field.

The thesis takes refined solid paraffin, liquid paraffin and dodecyl alcohol molten mixture as environmentally friendly decorative materials. By adding chlorinated paraffin, graphite fibre and other materials to improve its phase change sensitivity, high-performance composite phase change materials are prepared for use in construction under construction. Combining high-performance composite phase-change materials and interior decoration energy-saving and environmentally friendly decorative material systems, a set of indoor self-temperature-adjusting energy-saving and environmentally friendly decorative material systems based on composite phase-change materials was designed. The green energy-saving and environment-friendly decorative material system can cause the phase change material to undergo phase change to absorb or release heat when the season changes or the indoor temperature fluctuates, thereby realising self-adjustment of the indoor temperature and reducing energy consumption for cooling or heating. It is practical and efficient when combined with decorative ceilings and environmental protection integrated internal partition wall panels for interior decoration.

Many broadly neutralizing antibodies (bnAbs) bind to conserved areas of the hemagglutinin (HA) stalk region and can inhibit the low pH induced HA conformational changes necessary for viral membrane fusion activity. We developed and evaluated a high-throughput virus-free and cell-free ELISA based low pH induced HA Conformational Change Inhibition Antibody Detection Assay (HCCIA) and a complementary proteinase susceptibility assay. Human serum samples (n = 150) were tested by HCCIA using H3 recombinant HA. Optical density (OD) ratios of mAb HC31 at pH 4.8 to pH 7.0 ranged from 0.87 to 0.09. Our results demonstrated that low pH induced HA conformational change inhibition antibodies (CCI) neutralized multiple H3 strains after removal of head-binding antibodies. The results suggest that HCCIA can be utilized to detect and characterize CCI in sera, that are potentially broadly neutralizing, and serves as a useful tool for evaluating universal vaccine candidates targeting the HA stalk.

A hierarchical identity-based broadcast encryption (H-IBBE) scheme is an identity-based broadcast encryption (IBBE) scheme in a hierarchical environment. In order to obtain secure H-IBBE schemes in the quantum era, we propose an H-IBBE scheme based on the learning with errors problem assumption. Our scheme achieves indistinguishability from random under adaptive chosen-plaintext and chosen-identity attacks in the random oracle model.

The novel influenza A(H1N1)pdm09 virus caused an influenza pandemic in 2009. IgM, IgG, and IgA antibody responses to A(H1N1)pdm09 hemagglutinin (HA) following A(H1N1)pdm09 virus infection were analyzed to understand antibody isotype responses. Age-matched control sera collected from U.S. residents in 2007 and 2008 were used to establish baseline levels of cross-reactive antibodies. IgM responses often used as indicators of primary virus infection were mainly detected in young patient groups (≤5 years and 6 to 15 years old), not in older age groups, despite the genetic and antigenic differences between the HA of A(H1N1)pdm09 virus and pre-2009 seasonal H1N1 viruses. IgG and IgA responses to A(H1N1)pdm09 HA were detected in all age groups of infected persons. In persons 17 to 80 years old, paired acute- and convalescent-phase serum samples demonstrated ≥4-fold increases in the IgG and IgA responses to A(H1N1)pdm09 HA in 80% and 67% of A(H1N1)pdm09 virus-infected persons, respectively. The IgG antibody response to A(H1N1)pdm09 HA was cross-reactive with HAs from H1, H3, H5, and H13 subtypes, suggesting that infections with subtypes other than A(H1N1)pdm09 might result in false positives by enzyme-linked immunosorbent assay (ELISA). Lower sensitivity compared to hemagglutination inhibition and microneutralization assays and the detection of cross-reactive antibodies against homologous and heterologous subtype are major drawbacks for the application of ELISA in influenza serologic studies.

According to the value of PM2.5 in Langfang city in 2015, we propose a new prediction technique based on ARMA and improved BP neural network to forecast the PM2.5 concentrations. In order to prove the accuracy of prediction of PM2.5 concentration of the combined model, Two models considered in the study:ARMA+BP neural network combined model and ARMA+improved BP neural network combined model. The study showed that compared with the ARMA+BP neural network combined model, ARMA+improved BP neural network combined model can better predict the value of PM2.5 and the prediction error is relatively small.

Please cite this paper as: Fry et al. (2012) The first cases of 2009 pandemic influenza A (H1N1) virus infection in the United States: a serologic investigation demonstrating early transmission. Influenza and Other Respiratory Viruses 6(3), e48–e53. Background The first two laboratory-confirmed cases of 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were detected in San Diego (SD) and Imperial County (IC) in southern California, April 2009. Objectives To describe H1N1pdm09 infections and transmission early in the 2009 H1N1 pandemic. Patients/Methods We identified index case-patients from SD and IC with polymerase chain reaction (PCR)-confirmed H1N1pdm09 infections and investigated close contacts for a subset of case-patients from April 17–May 6, 2009. Acute and convalescent serum was collected. Serologic evidence for H1N1pdm09 infection was determined by microneutralization and hemagglutination inhibition assays. Results Among 75 close contacts of seven index case-patients, three reported illness onset prior to patient A or B, including two patient B contacts and a third with no links to patient A or B. Among the 69 close contacts with serum collected >14 days after the onset of index case symptoms, 23 (33%) were seropositive for H1N1pdm09, and 8 (35%) had no fever, cough, or sore throat. Among 15 household contacts, 8 (53%) were seropositive for H1N1pdm09. The proportion of contacts seropositive for H1N1pdm09 was highest in persons aged 5–24 years (50%) and lowest in persons aged ≥50 years (13%) (P = 0·07). Conclusions By the end of April 2009, before H1N1pdm09 was circulating widely in the community, a third of persons with close contact to confirmed H1N1pdm09 cases had H1N1pdm09 infection in SD and IC. Three unrelated clusters during March 21–30 suggest that transmission of H1N1pdm09 had begun earlier in southern California.

+T-cell immunity a b s t r a c t The development of pre-pandemic influenza A H5N1 vaccines that confer both antigen-sparing and crossclade protection are a high priority given the limited worldwide capacity for influenza vaccine production, and the antigenic and genetic heterogeneity of circulating H5N1 viruses. The inclusion of potent adjuvants in vaccine formulations may achieve both of these aims. Here we show that the addition of JVRS-100, an adjuvant consisting of cationic liposome–DNA complexes (CLDC) to a clade 1-derived H5N1 split vaccine induced significantly higher virus-specific antibody than unadjuvanted formulations, with a >30fold dose-sparing effect and induction of increased antigen-specific CD4+ T-cell responses in mice. All mice that received one dose of adjuvanted vaccine and subsequent H5N1 viral challenges exhibited mild illness, lower lung viral titers, undetectable spleen and brain viral titers, and 100% survival after either homologous clade 1 or heterologous clade 2 H5N1 viral challenges, whereas unadjuvanted vaccine recipients showed significantly increased weight loss, viral titers, and mortality. The protective immunity induced by JVRS-100 adjuvanted H5N1 vaccine was shown to last for over one year without significant waning. Thus, JVRS-100 adjuvanted H5N1 vaccine elicited enhanced humoral and T-cell responses, dosesparing, and cross-clade protection in mice. CLDC holds promise as an adjuvant for human pre-pandemic inactivated H5N1 vaccines.

Background Understanding transmissibility of influenza viruses within households is critical for guiding public health response to pandemics. We studied serologically confirmed infection and disease among household contacts of index case patients with 2009 pandemic influenza A (H1N1) virus (pH1N1) infection in a setting of minimal community pH1N1 transmission. Methods We defined index case patients as students and staff of a New York City high school with laboratory-confirmed pH1N1 infection during the earliest phase of the pH1N1 outbreak in April 2009. We visited households of index case patients twice, once in early May and again in June/July 2009. At each visit, household members (both index case patents and household contacts) provided serum samples and completed questionnaires about illness and possible risk factors. Serologic testing was performed using microneutralization and hemagglutination-inhibition assays. Results Of 79 eligible household contacts in 28 households, 19% had serologically confirmed pH1N1 infection, and 28% of those infected were asymptomatic. Serologically confirmed infection varied by age among household contacts: 36% of contacts younger than 10 years were infected, compared with 46% of contacts age 10-18 years, 8% of contacts aged 19-54 years, and 22% of contacts aged 55 years and older. Conclusions Infection rates were high for household contacts of persons with confirmed pH1N1, particularly for contacts aged 10-18 years, and asymptomatic infection was common. Efforts to reduce household transmission during influenza pandemics are important adjuncts to strategies to reduce community illness.

Matrix protein 2 (M2) of influenza A viruses is an attractive target for the development of broadly cross-protective influenza vaccines and therapeutic antibodies. The available evidence suggests that antibodies reactive to the natural tetrameric form of M2 proteins, rather than those to synthetic peptides of M2 ectodomain (M2e), best correlate with M2-mediated immune protection. However, the current ability to quantify strain-specific and/or subtype-cross-reactive M2 antibodies against the natural form of M2 antigens from influenza A viruses of different host origin is limited. In the present study, we generated a panel of 293FT transfected cell lines stably expressing full-length tetrameric forms of M2 molecules from human, avian and the swine-origin 2009 pandemic H1N1 influenza A virus, respectively, and developed an M2-293FT cell line-based flow cytometric assay (M2-FCA). Side-by-side comparison of M2-FCA with a synthetic M2e peptide-based indirect ELISA (M2e-ELISA) reveals that M2-FCA is highly efficient in quantifying both M2e sequence-specific and cross-reactive antibodies to the native form of M2 antigens. In contrast, promiscuity was evident when specificity and cross-reactivity of anti-M2 antibodies were assessed by M2e-ELISA. These results demonstrate that M2-FCA represents a rapid, simple and sensitive method to quantitatively assess specificity and cross-reactivity of anti-M2 antibodies after infection or vaccination.

Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential.

Herein, we report the draft genome sequences of six individual Staphylococcus epidermidis clones, cultivated from blood taken from different preterm neonatal sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom.

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future.

Avian H5N1 influenza viruses currently circulating in southeast Asia could potentially cause the next pandemic. However, currently licensed human vaccines are subtype-specific and do not protect against these H5N1 viruses. We aimed to develop an influenza vaccine and assessed its immunogenicity and efficacy to confer protection in BALB/c mice.We developed an egg-independent strategy to combat the avian influenza virus, because the virus is highly lethal to chickens and the maintenance of a constant supply of embryonated eggs would be difficult in a pandemic. We used a replication-incompetent, human adenoviral-vector-based, haemagglutinin subtype 5 influenza vaccine (HAd-H5HA), which induces both humoral and cell-mediated immune responses against avian H5N1 influenza viruses isolated from people.Immunisation of mice with HAd-H5HA provided effective protection from H5N1 disease, death, and primary viral replication (p0.0001) against antigenically distinct strains of H5N1 influenza viruses. Unlike the recombinant H5HA vaccine, which is based on a traditional subunit vaccine approach, HAd-H5HA vaccine induced a three-fold to eight-fold increase in HA-518-epitope-specific interferon-gamma-secreting CD8 T cells (p=0.01).Our findings highlight the potential of an Ad-vector-based delivery system, which is both egg-independent and adjuvant-independent and offers stockpiling options for the development of a pandemic influenza vaccine.

To prepare candidate influenza pandemic vaccines, we are developing an approach based on reassortment of antigenically appropriate nonpathogenic avian viruses of different subtypes (H5, H9, H7) with the cold-adapted master strain (MS) A/Leningrad/134/17/57 (Len/17) that is currently used in Russia for preparing licensed live attenuated vaccines for adults and children. In the present study, reassortants between A/Duck/Potsdam/1402-6/86(H5N2) (H5N2-wt) and Len/17 were obtained. One of the clones, A/17/Duck/Potsdam/86-92(H5N2) (Len17/H5), was chosen for further detailed genetic and antigenic analysis. Len17/H5 inherited the HA gene from the H5N2-wt and all other genes from Len/17 (7:1 genome composition). The HA gene sequence of Len17/H5 was identical to that of the parent H5N2-wt virus. The antigenic profile of the reassortant virus was similar to that of the H5N2-wt parent strain in the hemagglutination-inhibition (HI) test with a panel of antisera to different avian and human H5 viruses. The reassortant demonstrated high growth ability (9.3+0.3 lg EID50/ml) in embryonated hens' eggs (CE) at optimal (34 °C) temperature, comparable with that of the parent Len/17 MS. Also, Len17/H5 demonstrated cold-adapted (ca) and temperature-sensitive (ts) phenotypes similar to those of Len/17 and was attenuated for mice.

Background: In February 2003, highly pathogenic avian influenza A H5N1 viruses reemerged in humans. Despite repeated outbreaks in domestic poultry in Hong Kong since 1999, this was the first isolation of H5N1 from humans since the outbreak in Hong Kong in 1997, which resulted in 18 human cases and 6 deaths. Methods: To better understand the antigenic relationship between the 2003 H5N1 human virus A/Hong Kong/213/03 (HK/213) and other H5 viruses, post- infection ferret sera or post-infection human sera were tested for reactivity by hemagglutination- inhibition and microneutralization assays with H5N1 viruses circulating in Hong Kong or elsewhere in Asia since 1997. Results: The H5N1 virus isolated from a 9-year-old male in Hong Kong was antigenically distinguishable from recent H5N1 viruses isolated from wild birds in Hong Kong and from the human 1997 H5N1 viruses, using post-infection ferret sera. Likewise, sera from this case patient, collected 22 days post-symptom onset, reacted to high titers with the homologous HK/213 virus, but gave eightfold lower titers with A/Hong Kong/156/97, and other H5 viruses. Conclusion: These results suggest that this recent human H5N1 virus is antigenically distinguishable from current and previously circulating H5N1 viruses from Asia, including the viruses previously isolated from humans. D 2004 Elsevier B.V. All rights reserved.

The outbreak of avian influenza H5N1 in Hong Kong in 1997 raised concerns about the potential for the H5 subtype to cause a human pandemic. In 2001 a new H5N1 virus, A/Duck Meat/Anyang/AVL-1/2001 (A/Dkmt), was isolated from imported duck meat in Korea. The pathogenesis of this virus was investigated in mice. A/Dkmt virus had low infectivity but was lethal for mice at high doses, and at lethal doses, the virus replicated in the brains of infected mice. A/Dkmt virus cross-reacted poorly with ferret antisera raised against human H5N1 viruses, but prior infection with A/Dkmt virus protected mice from death after secondary infection with human H5N1 virus.

Influenza vaccines capable of inducing both systemic and mucosal antibody responses are highly desirable. Optimal induction of mucosal IgA is accomplished by mucosal delivery of vaccine. Mucosal adjuvants may improve the immunogenicity and efficacy of vaccines delivered by this route. Here, we compare the adjuvant activities of a mutant of heat-labile enterotoxin from Escherichia coli [LT(R192G)] with those of the wildtype LT (wtLT) for oral vaccination with inactivated influenza vaccine in BALB/c mice. Compared with administration of oral influenza vaccine alone, co-administration of vaccine with LT(R192G) provided enhanced protection from infection in the upper and lower respiratory tract equivalent to and at similar doses as that obtained with wtLT. Likewise, LT(R192G) augmented virus-specific IgG and IgA responses in serum, lung and nasal washes and the numbers of virus-specific antibody-forming cells in spleen, lung and Peyer’s patches in a manner comparable to wtLT. Virus-specific splenic CD4 + cells from mice administered oral vaccine with either adjuvant produced a mixed Th1- and Th2-type cytokine response pattern. Taken together, these results indicate that LT(R192G), like wtLT, is a potent adjuvant for oral vaccination of mice with influenza vaccine.