Pathogenicity of an H5N1 avian influenza virus isolated in Vietnam in 2012 and reliability of conjunctival samples for diagnosis of infection

The continued spread of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 among poultry in Vietnam poses a potential threat to animals and public health. To evaluate the pathogenicity of a 2012 H5N1 HPAIV isolate and to assess the utility of conjunctival swabs for viral detection and isolation in surveillance, an experimental infection with HPAIV subtype H5N1 was carried out in domestic ducks. Ducks were infected with 10[superscript 7.2] TCID[subscript 50] of A/duck/Vietnam/QB1207/2012 (H5N1), which was isolated from a moribund domestic duck. In the infected ducks, clinical signs of disease, including neurological disorder, were observed. Ducks started to die at 3 days-post-infection (dpi), and the study mortality reached 67%. Viruses were recovered from oropharyngeal and conjunctival swabs until 7 dpi and from cloacal swabs until 4 dpi. In the ducks that died or were sacrificed on 3, 5, or 6 dpi, viruses were recovered from lung, brain, heart, pancreas and intestine, among which the highest virus titers were in the lung, brain or heart. Results of virus titration were confirmed by real-time RT-PCR. Genetic and phylogenetic analysis of the HA gene revealed that the isolate belongs to clade 2.3.2.1 similarly to the H5N1 viruses isolated in Vietnam in 2012. The present study demonstrated that this recent HPAI H5N1 virus of clade 2.3.2.1 could replicate efficiently in the systemic organs, including the brain, and cause severe disease with neurological symptoms in domestic ducks. Therefore, this HPAI H5N1 virus seems to retain the neurotrophic feature and has further developed properties of shedding virus from the oropharynx and conjunctiva in addition to the cloaca, potentially posing a higher risk of virus spread through cross-contact and/or environmental transmission. Continued surveillance and diagnostic programs using conjunctival swabs in the field would further verify the apparent reliability of conjunctival samples for the detection of AIV.Japan Society for the Promotion of Science (Grant-in-Aid for Bilateral Joint Projects)Heiwa Nakajima FoundationNational Institute of Allergy and Infectious Diseases (U.S.) (Contract HHSN2662007000010C

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A method based on L-BFGS to solve constrained complex-valued ICA

Complex-valued independent component analysis (ICA) is a celebrated method in blind separation of complex-valued signals. In this paper, we propose to transform the constrained optimization problems of complex-valued ICA into unconstrained optimization problems which can be solved by limited-memory Broyden–Fletcher–Goldfarb–Shanno update (L-BFGS). As opposed to previous approaches, the proposed method does not apply any restriction on the Hessian matrix of ICA cost function. It can separate mixed sub-Gaussian, super-Gaussian, circular, and non-circular sources. Simulations show promising results.NRF (Natl Research Foundation, S’pore)Accepted versio

Avian influenza in Vietnam: current status and complementary of surveillance protocols and epidemiological studies (2007–2011)

Since 2003, H5N1 highly pathogenic avian influenza (HPAI) epidemic has been emphasizing the need for effective animal health surveillance systems to prevent an influenza pandemic. In some countries ad hoc surveillance initiatives funded by international donors have been implemented but without an appropriate link with the situation in the field and with the public institutions responsible for health monitoring. On the other hand other projects have strengthened the structures already in place. The aim of this study was to make an inven­tory of HPAI surveillance activities in poultry in Vietnam to assess the complementarity of national systems (funded by the Vietnamese Government) and programs implemented by international donors. Results showed that the various surveil­lance setups, epidemiological studies and research projects have been generally complementary and covered the country homogeneously. However, the new government policies have been mostly redefined without assessing previous activities because of insufficient data to assess the implemented pro­jects, including their impacts. There was also a malfunction of the passive surveillance systems as there was limited informa­tion feedback to field actors. It is therefore essential to set up effective surveillance activities combined with passive surveil­lance to manage HPAI risk in Vietnam

A genome-wide association study using a Vietnamese landrace panel of rice (Oryza sativa) reveals new QTLs controlling panicle morphological traits

ContextYield improvement is an important issue for rice breeding. Panicle architecture is one of the key components of rice yield and exhibits a large diversity. To identify the morphological and genetic determinants of panicle architecture, we performed a detailed phenotypic analysis and a genome-wide association study (GWAS) using an original panel of Vietnamese landraces.ResultsUsing a newly developed image analysis tool, morphological traits of the panicles were scored over two years: rachis length; primary, secondary and tertiary branch number; average length of primary and secondary branches; average length of internode on rachis and primary branch. We observed a high contribution of spikelet number and secondary branch number per panicle to the overall phenotypic diversity in the dataset. Twenty-nine stable QTLs associated with seven traits were detected through GWAS over the two years. Some of these QTLs were associated with genes already implicated in panicle development. Importantly, the present study revealed the existence of new QTLs associated with the spikelet number, secondary branch number and primary branch number traits.ConclusionsOur phenotypic analysis of panicle architecture variation suggests that with the panel of samples used, morphological diversity depends largely on the balance between indeterminate vs. determinate axillary meristem fate on primary branches, supporting the notion of differences in axillary meristem fate between rachis and primary branches. Our genome-wide association study led to the identification of numerous genomic sites covering all the traits studied and will be of interest for breeding programs aimed at improving yield. The new QTLs detected in this study provide a basis for the identification of new genes controlling panicle development and yield in rice