Immune escape #adaptive #mutations in the #H7N9 #avian #influenza #hemagglutinin protein increase virus #replication #fitness and decrease #pandemic #potential (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Immune escape adaptive mutations in the H7N9 avian influenza hemagglutinin protein increase virus replication fitness and decrease pandemic potential

Pengxiang Chang, Joshua E. Sealy, Jean-Remy Sadeyen, Sushant Bhat, Deimante Lukosaityte, Yipeng Sun, Munir Iqbal

DOI: 10.1128/JVI.00216-20

 

ABSTRACT

H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T), 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in the field isolates in 2019. To investigate the potential threat of the serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo. They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in HA protein might pose a reduced pandemic risk but remain a heightened threat for poultry.

 

IMPORTANCE

Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in the virus-specific antiserum give rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunised or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chick embryo as well as (ii) increased acid and thermal stability, but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing indicated mutations remain a significant risk to the poultry due to antigenic drift and improved fitness for poultry.

Copyright © 2020 Chang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Avian Influenza; H7N9; Poultry; Evolution.

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#Evolution and #Antigenic #Drift of #Influenza A (#H7N9) Viruses, #China, 2017–2019 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 8—August 2020 | Dispatch

Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019

Jiahao Zhang1, Hejia Ye1, Huanan Li1, Kaixiong Ma, Weihong Qiu, Yiqun Chen, Ziwen Qiu, Bo Li, Weixin Jia, Zhaoping Liang, Ming Liao  , and Wenbao Qi

Author affiliations: College of Veterinary Medicine, South China Agricultural University, Guangzhou, China (J. Zhang, H. Li, K. Ma, Y. Chen, Z. Qiu, B. Li, W. Jia, M. Liao, W. Qi); National Avian Influenza Para-Reference Laboratory, Ministry of Agriculture and Rural Affairs of the People’s Republic of China, Guangzhou (J. Zhang, H. Li, W. Jia, M. Liao, W. Qi); Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs of the People’s Republic of China, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, National Development and Reform Commission, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou (J. Zhang, W. Jia, M. Liao, W. Qi); Guangzhou South China Biological Medicine Co., Ltd, Guangzhou (H. Ye, W. Qiu, Z. Liang); Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou (W. Jia, M. Liao, W. Qi)

 

Abstract

After a sharp decrease of influenza A(H7N9) virus in China in 2018, highly pathogenic H7N9 viruses re-emerged in 2019. These H7N9 variants exhibited a new predominant subclade and had been cocirculating at a low level in eastern and northeastern China. Several immune escape mutations and antigenic drift were observed in H7N9 variants.

Keywords: Avian Influenza; H7N9; China.

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Development of a #monoclonal #antibody‐based antigen capture #ELISA for #detection of #H7N9 subtype #avian #influenza virus (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Development of a monoclonal antibody‐based antigen capture enzyme‐linked immunosorbent assay for detection of H7N9 subtype avian influenza virus

Fan Yang,  Yixin Xiao,  Fumin Liu,  Hangping Yao,  Nanping Wu,  Haibo Wu

First published: 10 July 2020 | DOI:  https://doi.org/10.1002/jmv.26292

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26292

 

Abstract

In order to establish a rapid detection method for H7N9 avian influenza virus (AIV), monoclonal antibodies (mAbs) against hemagglutinin (HA) of H7N9 were developed to establish an antigen capture enzyme‐linked immunosorbent assay (AC‐ELISA). AC‐ELISA achieved high specificity and sensitivity, with a detection limit of 3.9 ng/ml for H7N9 HA protein (A/Zhejiang/DTID‐ZJU01/2013), and 2‐2 HA unit/100 μl for live H7N9 AIV. The inter‐ and intra‐assay coefficient of variation was less than 10%. Compared with conventional virus isolation detection, the sensitivity and specificity were 94.96% and 88.24%, respectively. AC‐ELISA proved to be a rapid and practical technique for detection of H7N9 AIV.

This article is protected by copyright. All rights reserved.

Keywords: Avian Influenza; H7N9; Monoclonal antibodies; Diagnostic tests.

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Induction of Cross-Group Broadly Reactive #Antibody #Response by Natural #H7N9 #Avian #Influenza Virus #Infection and Immunization With Inactivated H7N9 #Vaccine in #Chickens (Transbound Emerg Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transbound Emerg Dis. 2020 Jun 29. doi: 10.1111/tbed.13705. Online ahead of print.

Induction of Cross-Group Broadly Reactive Antibody Response by Natural H7N9 Avian Influenza Virus Infection and Immunization With Inactivated H7N9 Vaccine in Chickens

Zenglei Hu 1 2 3 4, Lei Shi 3 4, Naiqing Xu 3 4, Xiaoquan Wang 3 4, Jiao Hu 3 4, Jiangyan Zhao 3 4, Xiaowen Liu 3 4, Shunlin Hu 3 4, Min Gu 3 4, Yongzhong Cao 1 2, Xiufan Liu 1 2 3 4

Affiliations: 1 Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China. 2 Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, China. 3 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, China. 4 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.

PMID: 32602258 DOI: 10.1111/tbed.13705

 

Abstract

Pre-existing immunity against the conserved hemagglutinin (HA) stalk underlies the elicitation of cross-group antibody induced by natural H7N9 virus infection and immunization in humans. However, whether broadly reactive antibodies can be induced by H7N9 infection and immunization in the absence of pre-existing stalk-specific immunity is unclear. In this study, antibody response induced by H7N9 virus infection and immunization with inactivated and viral-vectored H7N9 vaccines in naïve chickens was analyzed. The results showed that H7N9 infection and immunization with inactivated vaccine resulted in potent induction of hemagglutination-inhibition (HI), virus neutralization (VN) and HA-binding antibodies, whereas Newcastle disease virus (NDV)-vectored H7N9 vaccine induced marginal HI and VN titers but high levels of HA-binding antibody. In addition, H7N9 infection and immunization induced stalk-specific antibodies in naïve chickens and these antibodies recognized different epitopes in the stalk. Virus infection and immunization with inactivated vaccine elicited antibodies cross-reactive with both group 1 and group 2 HAs, while antibodies induced by NDV-H7N9 vaccination showed a narrower cross-reactivity within group 2. Moreover, only homologous neutralizing activity of the sera against H7N9 virus was observed, and cross-binding antibodies did not show heterosubtypic neutralizing activity. Our results indicated that cross-group binding but non-neutralizing antibodies primarily targeting the stalk can be induced by natural H7N9 infection and immunization with inactivated vaccine in naïve chickens. This suggests that at least in a naïve chicken model, pre-existing stalk-specific immunity is not required for induction of broadly reactive antibodies. Additionally, H7N9-based immunogens may be explored as vaccine candidates or as a prime component to induce broadly protective influenza immunity.

Keywords: H7N9 avian influenza; HA stalk; antibody response; broadly-reactive; cross-group; immunization; virus infection.

This article is protected by copyright. All rights reserved.

Keywords: Avian Influenza; H7N9; Vaccines; Animal models.

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#Geographical #Variation in the #Risk of #H7N9 #Human #Infections in #China: Implications for Risk-Based #Surveillance (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2020 Jun 25;10(1):10372. doi: 10.1038/s41598-020-66359-1.

Geographical Variation in the Risk of H7N9 Human Infections in China: Implications for Risk-Based Surveillance

Xiaoyan Zhou 1, Lu Gao 2, Youming Wang 2, Yin Li 2 3, Yi Zhang 2, Chaojian Shen 2, Ailing Liu 2, Qi Yu 4, Wenyi Zhang 5, Alexander Pekin 6, Fusheng Guo 7, Carl Smith 8, Archie C A Clements 9 10, John Edwards 6 2 3, Baoxu Huang 11, Ricardo J Soares Magalhães 6 12

Affiliations collapse: 1 School of Veterinary Science, The University of Queensland, Brisbane, Australia. zhouxy339@outlook.com. 2 China Animal Health and Epidemiology Centre, Ministry of Agriculture and Rural Affairs, Qingdao, PR China. 3 School of Veterinary and Biomedical Sciences, Murdoch University, Perth, Australia. 4 Beijing Center for Animal Disease Prevention and Control, Beijing, PR China. 5 Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing, PR China.  6 School of Veterinary Science, The University of Queensland, Brisbane, Australia. 7 Food and Agriculture Organization of the United Nations (FAO), Bangkok, Thailand. 8 School of Business, The University of Queensland, Brisbane, Australia. 9 Faculty of Health Sciences, Curtin University, Perth, Australia. 10 Telethon Kids Institute, Perth, Australia. 11 China Animal Health and Epidemiology Centre, Ministry of Agriculture and Rural Affairs, Qingdao, PR China. huangbx@cahec.cn. 12 Child Health Research Centre, The University of Queensland, Brisbane, Australia.

PMID: 32587266 DOI: 10.1038/s41598-020-66359-1

 

Abstract

The influenza A (H7N9) subtype remains a public health problem in China affecting individuals in contact with live poultry, particularly at live bird markets. Despite enhanced surveillance and biosecurity at LBMs H7N9 viruses are now more widespread in China. This study aims to quantify the temporal relationship between poultry surveillance results and the onset of human H7N9 infections during 2013-2017 and to estimate risk factors associated with geographical risk of H7N9 human infections in counties in Southeast China. Our results suggest that poultry surveillance data can potentially be used as early warning indicators for human H7N9 notifications. Furthermore, we found that human H7N9 incidence at county-level was significantly associated with the presence of wholesale LBMs, the density of retail LBMs, the presence of poultry virological positives, poultry movements from high-risk areas, as well as chicken population density and human population density. The results of this study can influence the current AI H7N9 control program by supporting the integration of poultry surveillance data with human H7N9 notifications as an early warning of the timing and areas at risk for human infection. The findings also highlight areas in China where monitoring of poultry movement and poultry infections could be prioritized.

Keywords: Avian Influenza; H7N9; Human; Poultry; China.

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A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic #Stability of a New Potential #Pandemic #H7N9 Live Attenuated #Influenza #Vaccine in Healthy Adults (Vaccines (Basel), abstract)

[Source: Vaccines (Basel), full page: (LINK). Abstract, edited.]

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

by  Irina Kiseleva 1,* , Irina Isakova-Sivak 1 , Marina Stukova 2, Marianna Erofeeva 2, Svetlana Donina 1, Natalie Larionova 1, Elena Krutikova 1, Ekaterina Bazhenova 1 , Ekaterina Stepanova 1 , Kirill Vasilyev 2 , Victoria Matyushenko 1, Marina Krylova 3, Julia Galatonova 3, Aleksey Ershov 3, Dmitry Lioznov 2, Erin Grace Sparrow 4 , Guido Torelli 4 and Larisa Rudenko 1

1 Federal State Budgetary Scientific Institution “Institute of Experimental Medicine”, 197376 St Petersburg, Russia; 2 Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 St Petersburg, Russia; 3 The Federal State Unitary Enterprise “Scientific and Production Association for Immunological Preparations “Microgen”, Ministry of Health of Russian Federation, 127473 Moscow, Russia; 4 World Health Organization, 1211 Geneva, Switzerland

*Author to whom correspondence should be addressed.

Vaccines 2020, 8(2), 296; https://doi.org/10.3390/vaccines8020296 (registering DOI)

Received: 1 May 2020 / Revised: 30 May 2020 / Accepted: 9 June 2020 / Published: 10 June 2020

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

 

Abstract

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

Keywords: H7N9 influenza; potential pandemic vaccine; LAIV; clinical trial; safety; stability; immune response; humoral immunity; cellular immunity

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Kiseleva, I.; Isakova-Sivak, I.; Stukova, M.; Erofeeva, M.; Donina, S.; Larionova, N.; Krutikova, E.; Bazhenova, E.; Stepanova, E.; Vasilyev, K.; Matyushenko, V.; Krylova, M.; Galatonova, J.; Ershov, A.; Lioznov, D.; Sparrow, E.G.; Torelli, G.; Rudenko, L. A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults. Vaccines 2020, 8, 296.

Keywords: A/H7N9; Avian Influenza; Vaccines.

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#Virus subtype-specific suppression of #MAVS aggregation and activation by #PB1-F2 protein of #influenza A (#H7N9) virus (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS |  PEER-REVIEWED | RESEARCH ARTICLE

Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus

Pak-Hin Hinson Cheung, Tak-Wang Terence Lee, Chun Kew, Honglin Chen, Kwok-Yung Yuen, Chi-Ping Chan , Dong-Yan Jin

Published: June 8, 2020 | DOI: https://doi.org/10.1371/journal.ppat.1008611 | This is an uncorrected proof.

 

Abstract

Human infection with avian influenza A (H5N1) and (H7N9) viruses causes severe respiratory diseases. PB1-F2 protein is a critical virulence factor that suppresses early type I interferon response, but the mechanism of its action in relation to high pathogenicity is not well understood. Here we show that PB1-F2 protein of H7N9 virus is a particularly potent suppressor of antiviral signaling through formation of protein aggregates on mitochondria and inhibition of TRIM31-MAVS interaction, leading to prevention of K63-polyubiquitination and aggregation of MAVS. Unaggregated MAVS accumulated on fragmented mitochondria is prone to degradation by both proteasomal and lysosomal pathways. These properties are proprietary to PB1-F2 of H7N9 virus but not shared by its counterpart in WSN virus. A recombinant virus deficient of PB1-F2 of H7N9 induces more interferon β in infected cells. Our findings reveal a subtype-specific mechanism for destabilization of MAVS and suppression of interferon response by PB1-F2 of H7N9 virus.

 

Author summary

Exactly why avian influenza A (H5N1) and (H7N9) viruses cause severe diseases in humans remains unclear. PB1-F2 protein encoded by influenza A virus is one virulence factor that might make a difference. In this study we show that PB1-F2 protein of H7N9 virus is particularly strong in the suppression of host antiviral defense. This was achieved by inhibiting a key protein in cell signaling named MAVS. PB1-F2 directs MAVS for degradation and prevents MAVS from forming protein aggregates required for full activation. A recombinant virus in which PB1-F2 of H7N9 has been deleted can activate host antiviral response robustly. Our findings reveal a novel mechanism by which PB1-F2 protein of H7N9 virus prevents MAVS aggregation and promotes MAVS degradation, leading to the suppression of host antiviral defense.

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Citation: Cheung P-HH, Lee T-WT, Kew C, Chen H, Yuen K-Y, Chan C-P, et al. (2020) Virus subtype-specific suppression of MAVS aggregation and activation by PB1-F2 protein of influenza A (H7N9) virus. PLoS Pathog 16(6): e1008611. https://doi.org/10.1371/journal.ppat.1008611

Editor: Peter Palese, Icahn School of Medicine at Mount Sinai, UNITED STATES

Received: February 6, 2020; Accepted: May 7, 2020; Published: June 8, 2020

Copyright: © 2020 Cheung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by Hong Kong Health and Medical Research Fund (15140662, HKM-15-M01, 19180812 and 19181002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: A/H7N9; Avian Influenza; Viral pathogenesis; Immunopathology.

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Live #Poultry #Market #Closure and #Avian #Influenza A (#H7N9) Infection in #Cities of #China, 2013-2017: An Ecological Study (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2020 May 24;20(1):369. doi: 10.1186/s12879-020-05091-7.

Live Poultry Market Closure and Avian Influenza A (H7N9) Infection in Cities of China, 2013-2017: An Ecological Study

Ying Chen 1 2, Jian Cheng 2, Zhiwei Xu 2, Wenbiao Hu 2, Jiahai Lu 3

Affiliations: 1 School of Public Health, Key Laboratory of Tropical Diseases Control of Ministry of Education, One Health Center of Excellence for Research &Training, Sun Yat-sen University, Guangzhou, China. 2 School of Public Health and Social Work, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. 3 School of Public Health, Key Laboratory of Tropical Diseases Control of Ministry of Education, One Health Center of Excellence for Research &Training, Sun Yat-sen University, Guangzhou, China. lujiahai@mail.sysu.edu.cn.

PMID: 32448137 DOI: 10.1186/s12879-020-05091-7

 

Abstract

Background:

Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9.

Method:

Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013 to 2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) model to select and quantify the dominant factor of H7N9 infection.

Results:

All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80 to 0.93. Respectively, a long-term LPMs closure for 10-13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p > 0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR = 0.35). Shenzhen implemented partial closure for first 3 epidemics (p > 0.05) and all closure in the latest 2 epidemic waves (RRR = 0.64).

Conclusion:

Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and rural remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure seems greater than that of meteorology on H7N9 transmission.

Keywords: Avian influenza A (H7N9); CARTs; Effect evaluation; Live poultry market closure.

Keywords: H7N9; Avian Influenza; Poultry; China; Poultry markets.

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#Pathogenesis of #influenza A(#H7N9) virus in aged non-human #primates (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Pathogenesis of influenza A(H7N9) virus in aged non-human primates

Satoshi Fukuyama, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Noriko Nakajima, Robert W Gregg, Hiroaki Katsura, Yuriko Tomita, Tadashi Maemura, Tiago Jose da Silva Lopes, Tokiko Watanabe, Jason E Shoemaker, Hideki Hasegawa, Seiya Yamayoshi, Yoshihiro Kawaoka

The Journal of Infectious Diseases, jiaa267, https://doi.org/10.1093/infdis/jiaa267

Published: 20 May 2020

 

Abstract

The avian influenza A(H7N9) virus has caused high mortality in humans, especially in the elderly; however, little is known about the mechanistic basis for this. In this study, we employed non-human primates to evaluate the effect of aging on the pathogenicity of A(H7N9) virus. We observed that A(H7N9) virus infection of aged animals (defined as 20–26 years) caused more severe symptoms than infection of young animals (defined as 2–3 years). In aged animals, lung inflammation was weak and virus infection was sustained. Although cytokine and chemokine expression in the lungs of most aged animals was lower than that in the lungs of young animals, one aged animal showed severe symptoms and dysregulated proinflammatory cytokine and chemokine production. These results suggest that attenuated or dysregulated immune responses in aged animals are responsible for the severe symptoms observed among elderly patients infected with A(H7N9) virus.

Aging, influenza, immune senescence, dysregulated immunity, non-human primate

Topic:  aging – cytokine – influenza – lung – immune response – chemokines – avian influenza – immunity – pneumonia – primates – virus diseases – infections – influenzavirus  a – mortality – viruses – older adult – pathogenicity – attenuation – influenza a virus, h7n9 subtype

Issue Section: Major Article

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© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Avian Influenza; H7N9; Immunopathology; Cytokines; Animal models.

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Use of PELC/CpG #Adjuvant for #Intranasal #Immunization with Recombinant #Hemagglutinin to Develop #H7N9 #Mucosal #Vaccine (Vaccines, abstract)

[Source: Vaccines, full page: (LINK). Abstract, edited.]

Use of PELC/CpG Adjuvant for Intranasal Immunization with Recombinant Hemagglutinin to Develop H7N9 Mucosal Vaccine

by  Ting-Hsuan Chen 1,†, Chung-Chu Chen 2,3,† , Ming-Hsi Huang 4 , Chung-Hsiung Huang 5, Jia-Tsrong Jan 6 and Suh-Chin Wu 1,7,*

1 Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan; 2 Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu 30071, Taiwan; 3 Teaching Center of Natural Science, Minghsin University of Science and Technology, Hsinchu 30401, Taiwan; 4 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, Taiwan; 5 Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan; 6 Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan; 7 Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan

*Author to whom correspondence should be addressed.

†These authors contributed equally for this work.

Vaccines 2020, 8(2), 240; https://doi.org/10.3390/vaccines8020240 (registering DOI)

Received: 30 April 2020 / Revised: 12 May 2020 / Accepted: 20 May 2020 / Published: 21 May 2020

(This article belongs to the Special Issue Vaccinology of Influenza Infection)

 

Abstract

Human infections with H7N9 avian influenza A virus can result in severe diseases with high mortality. Developing an effective vaccine is urgently needed to prevent its pandemic potential. Vaccine delivery routes via mucosal surfaces are known to elicit mucosal immune responses such as secretory IgA antibodies in mucosal fluids, thus providing first-line protection at infection sites. PEG-b-PLACL (PELC) is a squalene-based oil-in-water emulsion adjuvant system that can enhance antigen penetration and uptake in nasal mucosal layers with enhanced mucin interactions. In this study, intranasal immunizations with recombinant H7 (rH7) proteins with a PELC/CpG adjuvant, as compared to the use of poly (I:C) or bacterial flagellin adjuvant, elicited higher titers of H7-specific IgG, IgA, hemagglutination inhibition, and neutralizing antibodies in sera, and increased numbers of H7-specific IgG- and IgA-antibody secreting cells in the spleen. Both PELC/CpG and poly (I:C) adjuvants at a dose as low as 5 μg HA provided an 80% survival rate against live virus challenges, but a lower degree of PELC/CpG-induced Th17 responses was observed. Therefore, the mucosal delivery of rH7 proteins formulated in a PELC/CpG adjuvant can be used for H7N9 mucosal vaccine development.

Keywords: H7N9; intranasal; adjuvant; mucosal vaccine

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Chen, T.-H.; Chen, C.-C.; Huang, M.-H.; Huang, C.-H.; Jan, J.-T.; Wu, S.-C. Use of PELC/CpG Adjuvant for Intranasal Immunization with Recombinant Hemagglutinin to Develop H7N9 Mucosal Vaccine. Vaccines 2020, 8, 240.

Keywords: Avian Influenza; H7N9; Vaccines.

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