#Vaccination with viral #vectors expressing #NP, #M1 and chimeric #hemagglutinin induces broad protection against #influenza virus challenge in mice (Vaccine, abstract)

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

Vaccine. 2019 Aug 6. pii: S0264-410X(19)31016-3. doi: 10.1016/j.vaccine.2019.07.095. [Epub ahead of print]

Vaccination with viral vectors expressing NP, M1 and chimeric hemagglutinin induces broad protection against influenza virus challenge in mice.

Asthagiri Arunkumar G1, McMahon M2, Pavot V3, Aramouni M3, Ioannou A2, Lambe T3, Gilbert S4, Krammer F5.

Author information: 1 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA. 3 The Jenner Institute, University of Oxford, Oxford, UK. 4 The Jenner Institute, University of Oxford, Oxford, UK. Electronic address: sarah.gilbert@ndm.ox.ac.uk. 5 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: florian.krammer@mssm.edu.

 

Abstract

Seasonal influenza virus infections cause significant morbidity and mortality every year. Annual influenza virus vaccines are effective but only when well matched with circulating strains. Therefore, there is an urgent need for better vaccines that induce broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach to design such vaccines is based on targeting conserved regions of the influenza virus hemagglutinin. Sequential vaccination with chimeric hemagglutinin constructs can refocus antibody responses towards the conserved immunosubdominant stalk domain of the hemagglutinin, rather than the variable immunodominant head. A complementary approach for a universal influenza A virus vaccine is to induce T-cell responses to conserved internal influenza virus antigens. For this purpose, replication deficient recombinant viral vectors based on Chimpanzee Adenovirus Oxford 1 and Modified Vaccinia Ankara virus are used to express the viral nucleoprotein and the matrix protein 1. In this study, we combined these two strategies and evaluated the efficacy of viral vectors expressing both chimeric hemagglutinin and nucleoprotein plus matrix protein 1 in a mouse model against challenge with group 2 influenza viruses including H3N2, H7N9 and H10N8. We found that vectored vaccines expressing both sets of antigens provided enhanced protection against H3N2 virus challenge when compared to vaccination with viral vectors expressing only one set of antigens. Vaccine induced antibody responses against divergent group 2 hemagglutinins, nucleoprotein and matrix protein 1 as well as robust T-cell responses to the nucleoprotein and matrix protein 1 were detected. Of note, it was observed that while antibodies to the H3 stalk were already boosted to high levels after two vaccinations with chimeric hemagglutinins (cHAs), three exposures were required to induce strong reactivity across subtypes. Overall, these results show that a combinations of different universal influenza virus vaccine strategies can induce broad antibody and T-cell responses and can provide increased protection against influenza.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Influenza; M1; NP; Stalk; T-cell immunity; Universal influenza virus vaccine

PMID: 31399277 DOI: 10.1016/j.vaccine.2019.07.095

Keywords: Influenza A; H3N2; H7N9; H10N8; Vaccines; Animal models.

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The #PB2 and M genes of #genotype S #H9N2 virus contribute to the enhanced #fitness of #H5Nx and #H7N9 #avian #influenza viruses in chickens (Virology, abstract)

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

Virology. 2019 Jul 8;535:218-226. doi: 10.1016/j.virol.2019.07.001. [Epub ahead of print]

The PB2 and M genes of genotype S H9N2 virus contribute to the enhanced fitness of H5Nx and H7N9 avian influenza viruses in chickens.

Hao X1, Wang X1, Hu J1, Gu M1, Wang J1, Deng Y1, Jiang D1, He D1, Xu H1, Yang Y1, Hu Z1, Chen S1, Hu S1, Liu X1, Shang S1, Peng D1, Jiao X2, Liu X3.

Author information: 1 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. 3 Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China, Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: xfliu@yzu.edu.cn.

 

Abstract

Genotype S H9N2 viruses frequently donate their internal genes to facilitate the generation of novel influenza viruses, e.g., H5N6, H7N9, and H10N8, which have caused human infection. Genotype S was originated from the replacement of F/98-like M and PB2 genes of the genotype H with those from G1-like lineage. However, whether this gene substitution will influence the viral fitness of emerging influenza viruses remains unclear. We found that H5Nx and H7N9 viruses with G1-like PB2 or M gene exhibited higher virulence and replication than those with F/98-like PB2 or M in chickens. We also determined the functional significance of G1-like PB2 in conferring increased polymerase activity and improved nucleus transportation efficiency, and facilitated RNP nuclear export by G1-like M. Our results suggest that G1-like PB2 and M genes optimize viral fitness, and thus play a crucial role in the genesis of emerging influenza viruses that cause rising prevalence in chickens.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Avian influenza virus; Chickens; G1-like PB2 and M; H5Nx; H7N9; Viral fitness

PMID: 31325836  DOI: 10.1016/j.virol.2019.07.001

Keywords: Avian Influenza; H9N2; H5N6; H10N8; H7N9; Reassortant strain; Poultry.

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#mRNA #vaccines against #H10N8 and #H7N9 #influenza viruses of #pandemic #potential are immunogenic and well tolerated in healthy adults in phase 1 #RCTs (Vaccine, abstract)

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

Vaccine. 2019 May 9. pii: S0264-410X(19)30562-6. doi: 10.1016/j.vaccine.2019.04.074. [Epub ahead of print]

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials.

Feldman RA1, Fuhr R2, Smolenov I3, Mick Ribeiro A3, Panther L4, Watson M5, Senn JJ6, Smith M7, Almarsson Ӧ8, Pujar HS9, Laska ME3, Thompson J10, Zaks T11, Ciaramella G3.

Author information: 1 Miami Research Associates, 6280 Sunset Drive, Suite 600, So. Miami, FL 33143, USA. 2 PAREXEL International GmbH Klinikum Westend, House 18, Spandauer Damm 130, 14050 Berlin, Germany. Electronic address: Rainard.Fuhr@parexel.com. 3 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. 4 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Lori.Panther@modernatx.com. 5 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: mike.watson@modernatx.com. 6 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Joe.senn@modernatx.com. 7 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Mike.smith@modernatx.com. 8 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Orn.almarsson@modernatx.com. 9 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Hari.pujar@modernatx.com. 10 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: James.thompson@modernatx.com. 11 Moderna, 500 Technology Square, Cambridge, MA 02139, USA. Electronic address: Tal.zaks@modernatx.com.

 

Abstract

BACKGROUND:

We evaluated safety and immunogenicity of the first mRNA vaccines against potentially pandemic avian H10N8 and H7N9 influenza viruses.

METHODS:

Two randomized, placebo-controlled, double-blind, phase 1 clinical trials enrolled participants between December 2015 and August 2017 at single centers in Germany (H10N8) and USA (H7N9). Healthy adults (ages 18-64 years for H10N8 study; 18-49 years for H7N9 study) participated. Participants received vaccine or placebo in a 2-dose vaccination series 3 weeks apart. H10N8 intramuscular (IM) dose levels of 25, 50, 75, 100, and 400 µg and intradermal dose levels of 25 and 50 µg were evaluated. H7N9 IM 10-, 25-, and 50-µg dose levels were evaluated; 2-dose series 6 months apart was also evaluated. Primary endpoints were safety (adverse events) and tolerability. Secondary immunogenicity outcomes included humoral (hemagglutination inhibition [HAI], microneutralization [MN] assays) and cell-mediated responses (ELISPOT assay).

RESULTS:

H10N8 and H7N9 mRNA IM vaccines demonstrated favorable safety and reactogenicity profiles. No vaccine-related serious adverse event was reported. For H10N8 (N = 201), 100-µg IM dose induced HAI titers ≥ 1:40 in 100% and MN titers ≥ 1:20 in 87.0% of participants. The 25-µg intradermal dose induced HAI titers > 1:40 in 64.7% of participants compared to 34.5% of participants receiving the IM dose. For H7N9 (N = 156), IM doses of 10, 25, and 50 µg achieved HAI titers ≥ 1:40 in 36.0%, 96.3%, and 89.7% of participants, respectively. MN titers ≥ 1:20 were achieved by 100% in the 10- and 25-µg groups and 96.6% in the 50-µg group. Seroconversion rates were 78.3% (HAI) and 87.0% (MN) for H10N8 (100 µg IM) and 96.3% (HAI) and 100% (MN) in H7N9 (50 µg). Significant cell-mediated responses were not detected in either study.

CONCLUSIONS:

The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses.

ClinicalTrials.gov NCT03076385 and NCT03345043.

Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

KEYWORDS: Immunogenicity; Pandemic influenza; Safety; Vaccines; mRNA

PMID: 31079849 DOI: 10.1016/j.vaccine.2019.04.074

Keywords: Avian Influenza; H7N9; H10N8; Vaccines.

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#Aerosol #exposure enhanced #infection of low pathogenic #avian #influenza viruses in #chickens (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Jan;66(1):435-444. doi: 10.1111/tbed.13039. Epub 2018 Nov 2.

Aerosol exposure enhanced infection of low pathogenic avian influenza viruses in chickens.

Jegede A1, Fu Q1, Lin M1,2, Kumar A2, Guan J1.

Author information: 1 Ottawa Laboratory (Fallowfield), Canadian Food Inspection Agency, Ottawa, Ontario, Canada. 2 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

 

Abstract

To assess the impact of different routes of inoculation on experimental infection of avian influenza (AI) viruses in chickens, this study compared virus replication and cytokine gene expression in respiratory and gastrointestinal organ tissues of chickens, which were inoculated with four low pathogenic subtypes, H6N1, H10N7, H10N8, and H13N6 AI viruses via the aerosol, intranasal, and oral routes respectively. Aerosol inoculation with the H6N1, H10N7, and H10N8 viruses significantly increased viral titres and upregulated the interferon (IFN)-γ, interleukin (IL)-6, and IL-1β genes in the trachea and lung tissues compared to intranasal or oral inoculation. Furthermore, one or two out of six chickens died following exposure to aerosolized H6N1 or H10N8 virus respectively. The H13N6 virus reached the lung via aerosol inoculation although failed to establish infection. Collectively, chickens were more susceptible to aerosolized AI viruses compared to intranasal or oral inoculation, and virus aerosols might post a significant threat to poultry health.

© 2018 Blackwell Verlag GmbH.

KEYWORDS: aerosols; and chickens; avian influenza viruses; cytokine gene expression; virus replication

PMID: 30307712 DOI: 10.1111/tbed.13039 [Indexed for MEDLINE]

Keywords: Avian Influenza; Animal models; Poultry; H6N1; H10N7; H10N8; H13N6.

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A Sandwich #ELISA for Detecting the #Hemagglutinin of #Avian #Influenza A (#H10N8) Virus (J Med Virol., abstract)

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

J Med Virol. 2018 Dec 29. doi: 10.1002/jmv.25387. [Epub ahead of print]

A Sandwich ELISA for Detecting the Hemagglutinin of Avian Influenza A (H10N8) Virus.

Chen L1,2, Ruan F1,2, Liu M3,4, Zhou J2, Song W5, Qin K2.

Author information: 1 Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, P. R. China. 2 National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health Commission of P. R. China, Beijing, P. R. China. 3 Shanghai Public Health Clinical Center, Fudan University, Shanghai, P. R. China. 4 Nanchang Center for Disease Control and Prevention, Nanchang, Jiangxi, P. R. China. 5 State Key Laboratory of Respiratory Disease; Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou, P. R. China.

 

Abstract

Novel influenza A virus (H10N8) infected human with fatality in China during 2013-2014. It is important to detect such non-prevalent subtype influenza A virus in clinic and regular surveillance in the early stage for effective control and prevention from the potential pandemic. Unavailability of convenient rapid diagnosis for this subtype virus in resources-limited setting is an obstacle for timely recognizing human case. In the present study, a panel of mouse H10 specific monoclonal antibodies (mAbs) was generated, two of which were used to develop a sandwich ELISA for detecting the hemagglutinin of avian influenza A (H10N8) virus. ELISA results showed high sensitivity with the lowest detection limit of 0.5HAU/50μl for live virus, which laid a foundation for clinic use as a promising diagnostic methodology.

This article is protected by copyright. All rights reserved.

KEYWORDS: H10 subtype; hemagglutinin; monoclonal antibody; sandwich ELISA

PMID: 30593681 DOI: 10.1002/jmv.25387

Keywords: Avian Influenza; H10N8; Diagnostic tests.

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#Human #infections with #avian #influenza viruses in mainland #China: A particular #risk for southeastern China (J Infect., abstract)

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

Human infections with avian influenza viruses in mainland China: A particular risk for southeastern China

Bin Xiang, Wenxian Zhu, Renrong You, Libin Chen, Yaling Li, Qiuyan Lin, Ming Liao, Tao Ren

DOI: https://doi.org/10.1016/j.jinf.2017.05.002

Published online: May 11, 2017 – Accepted:May 4, 2017

 

Abstract

As reported recently in this Journal, human infections with different subtypes of avian influenza viruses (AIVs) including H5N1, H5N6, H7N9, H10N8 and H9N2 have been identified in mainland China from 2005 to 2017.1–4Since the first H5N1 human case was confirmed in Hunan province in December 2005, a total of 46 human cases were reported in mainland China, of which 29 cases were fatal; while human infections with H5N6 virus was firstly documented in Sichuan province on March 3, 2014, 11 of 16 patients have been fatal (Table S1).

© 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Keywords: Avian Influenza; China; Human; H5N1; H5N6; H7N9; H10N8; H9N2.

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#Genetic characterization of the first detected #human case of #avian #influenza A (#H5N6) in #Anhui Province, East #China (Sci Rep., abstract)

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

Sci Rep. 2018 Oct 16;8(1):15282. doi: 10.1038/s41598-018-33356-4.

Genetic characterization of the first detected human case of avian influenza A (H5N6) in Anhui Province, East China.

He J1, Liu BY2, Gong L1, Chen Z2, Chen XL3, Hou S1, Yu JL1, Wu JB1, Xia ZC3, Latif A2, Gao R4, Su B5, Liu Y6.

Author information: 1 Anhui Center for Disease Control and Prevention, Hefei, China. 2 Department of Microbiology, Anhui Medical University, Hefei, China. 3 Xuancheng City Center for Disease Control and Prevention, Xuancheng, China. 4 National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. 5 Anhui Center for Disease Control and Prevention, Hefei, China. sub602@126.com. 6 Department of Microbiology, Anhui Medical University, Hefei, China. yliu16888@163.com.

 

Abstract

We compared complete genome sequences of two strains of an avian influenza A (H5N6) virus isolated from a patient in Anhui Province with those of other strains from GenBank and Global initiative on sharing all influenza data (GISAID). The HA gene of the isolated virus shared homology with that of A/chicken/Zhejiang/727155/2014 (H5N6) at the level of similarity of 98%. The six internal genes of the Anhui strains were close to those of H9N2 viruses from Zhejiang, Shandong, and Guangdong provinces, with a similarity of 99%. In addition, the similarity between the internal antigens (NP and MP) of the isolated H5N6 virus and H7N9 and H10N8 viruses was 99%. Based on the data of phylogenetic analysis, the H5N6 influenza virus isolated in Anhui Province belonged to clade 2.3.4.4. The virus was shown to have molecular characteristics of highly pathogenic avian influenza viruses, including eight glycosylation sites and an amino acid sequence of the HA protein cleavage site, PLRERRRKKR/GLF, containing multiple basic amino acids. Additionally, the stalk domain of the NA protein was found to have a deletion in NA stalk region (11 amino acids in N6, positions 58-68). Our study demonstrated that the H5N6 virus from Anhui Province represented a triple-reassortant virus and could be highly pathogenic to humans. The prevalence of this virus should be closely monitored.

PMID: 30327485 DOI: 10.1038/s41598-018-33356-4

Keywords: Avian Influenza; H5N6; Reassortant Strain; Human; China; Anhui; H7N9; H10N8.

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