Improving Cross- #Protection against #Influenza Virus Using Recombinant #Vaccinia #Vaccine Expressing NP and M2 Ectodomain Tandem Repeats (Virol Sin., abstract)

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

Improving Cross-Protection against Influenza Virus Using Recombinant Vaccinia Vaccine Expressing NP and M2 Ectodomain Tandem Repeats

Authors: Wenling Wang, Baoying Huang, Xiuping Wang, Wenjie Tan, Li Ruan

Research Article / First Online: 25 June 2019

 

Abstract

Conventional influenza vaccines need to be designed and manufactured yearly. However, they occasionally provide poor protection owing to antigenic mismatch. Hence, there is an urgent need to develop universal vaccines against influenza virus. Using nucleoprotein (NP) and extracellular domain of matrix protein 2 (M2e) genes from the influenza A virus A/Beijing/30/95 (H3N2), we constructed four recombinant vaccinia virus-based influenza vaccines carrying NP fused with one or four copies of M2e genes in different orders. The recombinant vaccinia viruses were used to immunize BALB/C mice. Humoral and cellular responses were measured, and then the immunized mice were challenged with the influenza A virus A/Puerto Rico/8/34 (PR8). NP-specific humoral response was elicited in mice immunized with recombinant vaccinia viruses carrying full-length NP, while robust M2e-specific humoral response was elicited only in the mice immunized with recombinant vaccinia viruses carrying multiple copies of M2e. All recombinant viruses elicited NP- and M2e-specific cellular immune responses in mice. Only immunization with RVJ-4M2eNP induced remarkably higher levels of IL-2 and IL-10 cytokines specific to M2e. Furthermore, RVJ-4M2eNP immunization provided the highest cross-protection in mice challenged with 20 MLD50 of PR8. Therefore, the cross-protection potentially correlates with both NP and M2e-specific humoral and cellular immune responses induced by RVJ-4M2eNP, which expresses a fusion antigen of full-length NP preceded by four M2e repeats. These results suggest that the rational fusion of NP and multiple M2e antigens is critical toward inducing protective immune responses, and the 4M2eNP fusion antigen may be employed to develop a universal influenza vaccine.

Keywords: Influenza A virus (IAV) – Cross-protection – Recombinant vaccinia virus – Conserved antigen

 

Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00138-9) contains supplementary material, which is available to authorized users.

 

Notes

Acknowledgements

This work was supported by grant from the National Key Plan for Scientific Research and Development of China (2016YFC1200200). The authors gratefully acknowledge Professor Xiangmin Zhang (Wayne State University, Detroit, MI USA) for the revision of the manuscript in English.

Author Contributions

RL and WW designed the experiments. WW, HB, and WX carried out the experiments. RL and WW analyzed the data. WW and TW wrote the paper. WW, TW checked and finalized the manuscript. All authors read and approved the final manuscript.

 

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The whole study was approved by the Administrative Committee on Animal Welfare of the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (Laboratory Animal Care and Use Committee Authorization, permit number 2016022910). All institutional and national guidelines for the care and use of laboratory animals were followed.

Keywords: Seasonal Influenza; H1N1; H3N2; Vaccines.

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#Genetic and #biological characteristics of #avian #influenza virus subtype #H1N8 in #environments related to live #poultry #markets in #China (BMC Infect Dis., abstract)

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

BMC Infect Dis. 2019 May 22;19(1):458. doi: 10.1186/s12879-019-4079-z.

Genetic and biological characteristics of avian influenza virus subtype H1N8 in environments related to live poultry markets in China.

Zhang Y1, Dong J1, Bo H1, Dong L1, Zou S1, Li X1, Shu Y1,2, Wang D3.

Author information: 1 Chinese National Influenza Centre, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention; WHO Collaborating Center for Reference and Research on Influenza; Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China. 2 Present Address: Public Health School (Shenzhen), Sun Yat-sen University, Guangzhou, China. 3 Chinese National Influenza Centre, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention; WHO Collaborating Center for Reference and Research on Influenza; Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China. dayanwang@cnic.org.cn.

 

Abstract

BACKGROUND:

Since 2008, avian influenza surveillance in poultry-related environments has been conducted annually in China. Samples have been collected from environments including live poultry markets, wild bird habitats, slaughterhouses, and poultry farms. Multiple subtypes of avian influenza virus have been identified based on environmental surveillance, and an H1N8 virus was isolated from the drinking water of a live poultry market.

METHODS:

Virus isolation was performed by inoculating influenza A-positive specimens into embryonated chicken eggs. Next-generation sequencing was used for whole-genome sequencing. A solid-phase binding assay was performed to test the virus receptor binding specificity. Trypsin dependence plaque formation assays and intravenous pathogenicity index tests were used to evaluate virus pathogenicity in vitro and in vivo, respectively. Different cell lines were chosen for comparison of virus replication capacity.

RESULTS:

According to the phylogenetic trees, the whole gene segments of the virus named A/Environment/Fujian/85144/2014(H1N8) were of Eurasian lineage. The HA, NA, PB1, and M genes showed the highest homology with those of H1N8 or H1N2 subtype viruses isolated from local domestic ducks, while the PB2, PA, NP and NS genes showed high similarity with the genes of H7N9 viruses detected in 2017 and 2018 in the same province. This virus presented an avian receptor binding preference. The plaque formation assay showed that it was a trypsin-dependent virus. The intravenous pathogenicity index (IVPI) in chickens was 0.02. The growth kinetics of the A/Environment/Fujian/85144/2014(H1N8) virus in different cell lines were similar to those of a human-origin virus, A/Brisbane/59/2007(H1N1), but lower than those of the control avian-origin and swine-origin viruses.

CONCLUSIONS:

The H1N8 virus was identified in avian influenza-related environments in China for the first time and may have served as a gene carrier involved in the evolution of the H7N9 virus in poultry. This work further emphasizes the importance of avian influenza virus surveillance, especially in live poultry markets (LPMs). Active surveillance of avian influenza in LPMs is a major pillar supporting avian influenza control and response.

KEYWORDS: Avian influenza virus; H1N8 subtype; Live poultry market

PMID: 31117981 DOI: 10.1186/s12879-019-4079-z

Keywords: Avian Influenza; Poultry; Live poultry markets; China; Reassortant strain; H1N1; H1N2; H7N9.

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A possible #European #origin of the #Spanish #influenza and the first attempts to reduce #mortality to combat superinfecting #bacteria: an opinion from a virologist and a military historian (Hum Vaccin Immunother., abstract)

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

Hum Vaccin Immunother. 2019 May 23:1-4. doi: 10.1080/21645515.2019.1607711. [Epub ahead of print]

A possible European origin of the Spanish influenza and the first attempts to reduce mortality to combat superinfecting bacteria: an opinion from a virologist and a military historian.

Oxford JS1, Gill D1.

Author information: 1a Blizard Institute, Queen Mary University London , Whitechapel, London.

 

Abstract

When we reconsider the virology and history of the Spanish Influenza Pandemic, the science of 2018 provides us with tools which did not exist at the time. Two such tools come to mind. The first lies in the field of ‘gain of function’ experiments. A potential pandemic virus, such as influenza A (H5N1), can be deliberately mutated in the laboratory in order to change its virulence and spreadability. Key mutations can then be identified. A second tool lies in phylogenetics, combined with molecular clock analysis. It shows that the 1918 pandemic virus first emerged in the years 1915-1916. We have revisited the literature published in Europe and the United States, and the notes left by physicians who lived at the time. In this, we have followed the words of the late Alfred Crosby: who wrote that “contemporary documentary evidence from qualified physicians” is the key to understanding where and how the first outbreaks occurred. In our view, the scientists working in Europe fulfill Crosby’s requirement for contemporary evidence of origin. Elsewhere, Crosby also suggested that “the physicians of 1918 were participants in the greatest failure of medical science in the twentieth century”. Ours is a different approach. We point to individual pathologists in the United States and in France, who strove to construct the first universal vaccines against influenza. Their efforts were not misdirected, because the ultimate cause of death in nearly all cases flowed from superinfections with respiratory bacteria.

KEYWORDS: Etaples Administrative District; Hospital Beds in the Great War; Hygiene in the Great War; Influenza Epidemics in 1917; New Vaccines; Spanish Influenza Origin

PMID: 31121112 DOI: 10.1080/21645515.2019.1607711

Keywords: Pandemic Influenza; H1N1; Spanish flu; History.

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A Site of #Vulnerability on the #Influenza Virus #Hemagglutinin Head Domain Trimer Interface (Cell, abstract)

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

Cell. 2019 May 16;177(5):1136-1152.e18. doi: 10.1016/j.cell.2019.04.011.

A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.

Bangaru S1, Lang S2, Schotsaert M3, Vanderven HA4, Zhu X2, Kose N5, Bombardi R5, Finn JA1, Kent SJ4, Gilchuk P5, Gilchuk I5, Turner HL2, García-Sastre A6, Li S7, Ward AB2, Wilson IA8, Crowe JE Jr9.

Author information: 1 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 2 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 3 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 4 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. 5 The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 6 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 7 Department of Medicine and Biomedical Sciences, School of Medicine, University of California, San Diego, CA 92093, USA. 8 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu. 9 Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.

 

Abstract

Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab’s extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: B-lymphocytes; antibodies; antibody-dependent cell cytotoxicity; antigen-antibody reactions; hemagglutinin glycoproteins; influenza A virus; influenza virus; monoclonal; viral

PMID: 31100268 DOI: 10.1016/j.cell.2019.04.011

Keywords: Influenza A; H1N1; H3N2; H5N1; H7N9; Monoclonal antibodies; Animal models.

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The #PA #Subunit of the #Influenza Virus #Polymerase Complex Affects #Replication and #Airborne #Transmission of the #H9N2 Subtype #Avian Influenza Virus (Viruses, abstract)

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

Viruses. 2019 Jan 9;11(1). pii: E40. doi: 10.3390/v11010040.

The PA Subunit of the Influenza Virus Polymerase Complex Affects Replication and Airborne Transmission of the H9N2 Subtype Avian Influenza Virus.

Hao M1,2, Han S3,4, Meng D5,6, Li R7, Lin J8, Wang M9, Zhou T10, Chai T11.

Author information: 1 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. mengchan1993@126.com. 2 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. mengchan1993@126.com. 3 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18763896230@163.com. 4 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. 18763896230@163.com. 5 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. iamli_z@126.com. 6 Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Taian 270016, China. iamli_z@126.com. 7 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. lirong19900129@163.com. 8 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18763806701@163.com. 9 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 18854937499@163.com. 10 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. 13864453175@163.com. 11 College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. chaitj117@163.com.

 

Abstract

The polymerase acidic (PA) protein is the third subunit of the influenza A virus polymerase. In recent years, studies have shown that PA plays an important role in overcoming the host species barrier and host adaptation of the avian influenza virus (AIV). The objective of this study was to elucidate the role of the PA subunit on the replication and airborne transmission of the H9N2 subtype AIV. By reverse genetics, a reassortant rSD01-PA was derived from the H9N2 subtype AIV A/Chicken/Shandong/01/2008 (SD01) by introducing the PA gene from the pandemic influenza A H1N1 virus A/swine/Shandong/07/2011 (SD07). Specific pathogen-free (SPF) chickens and guinea pigs were selected as the animal models for replication and aerosol transmission studies. Results show that rSD01-PA lost the ability of airborne transmission among SPF chickens because of the single substitution of the PA gene. However, rSD01-PA could infect guinea pigs through direct contact, while the parental strain SD01 could not, even though the infection of rSD01-PA could not be achieved through aerosol. In summary, our results indicate that the protein encoded by the PA gene plays a key role in replication and airborne transmission of the H9N2 subtype AIV.

KEYWORDS: H9N2 AIV; airborne transmission; pandemic 2009 H1N1 virus; reassortment; replication

PMID: 30634394 PMCID: PMC6356911 DOI: 10.3390/v11010040 [Indexed for MEDLINE]  Free PMC Article

Keywords: Avian Influenza; Swine Influenza; H1N1; H9N2; Reassortant strain.

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A brief #history of #birdflu (Philos Transact Roy Soc B., abstract)

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

Philos Trans R Soc Lond B Biol Sci. 2019 Jun 24;374(1775):20180257. doi: 10.1098/rstb.2018.0257.

A brief history of bird flu.

Lycett SJ1, Duchatel F1, Digard P1.

Author information: 1 The Roslin Institute, University of Edinburgh , Edinburgh , UK.

 

Abstract

In 1918, a strain of influenza A virus caused a human pandemic resulting in the deaths of 50 million people. A century later, with the advent of sequencing technology and corresponding phylogenetic methods, we know much more about the origins, evolution and epidemiology of influenza epidemics. Here we review the history of avian influenza viruses through the lens of their genetic makeup: from their relationship to human pandemic viruses, starting with the 1918 H1N1 strain, through to the highly pathogenic epidemics in birds and zoonoses up to 2018. We describe the genesis of novel influenza A virus strains by reassortment and evolution in wild and domestic bird populations, as well as the role of wild bird migration in their long-range spread. The emergence of highly pathogenic avian influenza viruses, and the zoonotic incursions of avian H5 and H7 viruses into humans over the last couple of decades are also described. The threat of a new avian influenza virus causing a human pandemic is still present today, although control in domestic avian populations can minimize the risk to human health. This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’. This issue is linked with the subsequent theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’.

KEYWORDS: avian influenza virus; epidemiology; pandemic; phylogenetics; zoonotic

PMID: 31056053 DOI: 10.1098/rstb.2018.0257

Keywords: Pandemic Influenza; Avian Influenza; Spanish Flu; H1N1; Human; Poultry; Wild Birds.

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#Birth #Cohort Effects in #Influenza #Surveillance #Data: Evidence that First Influenza Infection Affects Later Influenza-Associated Illness (J Infect Dis., abstract)

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

Birth Cohort Effects in Influenza Surveillance Data: Evidence that First Influenza Infection Affects Later Influenza-Associated Illness

Alicia P Budd, Lauren Beacham, Catherine B Smith, Rebecca J Garten, Carrie Reed, Krista Kniss, Desiree Mustaquim, Farida B Ahmad, Charisse N Cummings, Shikha Garg, Min Z Levine, Alicia M Fry, Lynnette Brammer

The Journal of Infectious Diseases, jiz201, https://doi.org/10.1093/infdis/jiz201

Published: 03 May 2019

 

Abstract

Background

The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons.

Methods

U.S. influenza virologic, hospitalization and mortality surveillance data during 2000-2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared to H1 predominant seasons during pre-pandemic versus pandemic and later periods were calculated for each cohort.

Results

During the pre-pandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, four cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons.

Discussion

Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in U.S. influenza surveillance data and differ between pre-pandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.

influenza, birth cohort, influenza hospitalization, influenza morality, influenza surveillance

Issue Section: Major Article

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; Pandemic Influenza; H1N1; H1N1pdm09; H3N2; USA.

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