#Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched #vaccines (JCI Insight, abstract)

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

JCI Insight. 2019 Nov 14;4(22). pii: 129035. doi: 10.1172/jci.insight.129035.

Hemagglutinin head-specific responses dominate over stem-specific responses following prime boost with mismatched vaccines.

Jegaskanda S1,2, Andrews SF3, Wheatley AK2,3, Yewdell JW4, McDermott AB3, Subbarao K1.

Author information: 1 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA. 2 Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 3 Vaccine Research Center and. 4 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, Maryland, USA.

 

Abstract

Broadly neutralizing Abs targeting the HA stem can provide broad protection against different influenza subtypes, raising the question of how best to elicit such Abs. We have previously demonstrated that vaccination with pandemic live-attenuated influenza vaccine (pLAIV) establishes immune memory for HA head-specific Abs. Here, we determine the extent to which matched versus mismatched LAIV-inactivated subunit vaccine (IIV) prime-boost vaccination elicits stem-specific memory B cells and Abs. We vaccinated African green monkeys with H5N1 pLAIV-pIIV or H5N1 pLAIV followed by seasonal IIV (sIIV) or with H5N1 pLAIV alone and measured Abs and HA-specific B cell responses. While we observed an increase in stem-specific memory B cells, head-specific memory B cell responses were substantially higher than stem-specific responses and were dominant even following boost with mismatched IIV. Neutralizing Abs against heterologous influenza viruses were undetectable. Head-specific B cells from draining lymph nodes exhibited germinal center markers, while stem-specific B cells found in the spleen and peripheral blood did not. Thus, although mismatched prime-boost generated a pool of stem-specific memory B cells, head-specific B cells and serum Abs substantially dominated the immune response. These findings have implications for including full-length native HA in prime-boost strategies intended to induce stem-specific Abs for universal influenza vaccination.

KEYWORDS: Infectious disease; Influenza; Vaccines

PMID: 31723058 DOI: 10.1172/jci.insight.129035

Keywords: Influenza A; H5N1; Vaccines.

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Highly Pathogenic and Low Pathogenic #Avian #Influenza #H5 Subtype Viruses in #WildBirds in #Ukraine (Avian Dis., abstract)

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

Avian Dis. 2019 Mar 1;63(sp1):235-245. doi: 10.1637/11880-042718.1.

Highly Pathogenic and Low Pathogenic Avian Influenza H5 Subtype Viruses in Wild Birds in Ukraine.

Muzyka D1, Rula O2, Tkachenko S2, Muzyka N3, Köthe S4, Pishchanskyi O2, Stegniy B2, Pantin-Jackwood M5, Beer M4.

Author information: 1 National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkiv, 61023, Ukraine, dmuzyka77@gmail.com. 2 National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkiv, 61023, Ukraine. 3 State Poultry Research Station, v. Birky, Kharkiv Region, 63422, Ukraine. 4 Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany. 5 Exotic and Emerging Avian Viral Diseases Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA 30677.

 

Abstract in English, Spanish

There have been three waves of highly pathogenic avian influenza (HPAI) outbreaks in commercial, backyard poultry, and wild birds in Ukraine. The first (2005-2006) and second (2008) waves were caused by H5N1 HPAI virus, with 45 outbreaks among commercial poultry (chickens) and backyard fowl (chickens, ducks, and geese) in four regions of Ukraine (AR Crimea, Kherson, Odesa, and Sumy Oblast). H5N1 HPAI viruses were isolated from dead wild birds: cormorants (Phalacrocorax carbo) and great crested grebes (Podiceps cristatus) in 2006 and 2008. The third HPAI wave consisted of nine outbreaks of H5N8 HPAI in wild and domestic birds, beginning in November 2016 in the central and south regions (Kherson, Odesa, Chernivtsi, Ternopil, and Mykolaiv Oblast). H5N8 HPAI virus was detected in dead mute swans (Cygnus olor), peacocks (Pavo cristatus) (in zoo), ruddy shelducks (Tadorna ferruginea), white-fronted geese (Anser albifrons), and from environmental samples in 2016 and 2017. Wide wild bird surveillance for avian influenza (AI) virus was conducted from 2006 to 2016 in Ukraine regions suspected of being intercontinental (north-south and east-west) flyways. A total of 21 511 samples were collected from 105 species of wild birds representing 27 families and 11 orders. Ninety-five avian influenza (AI) viruses were isolated (including one H5N2 LPAI virus in 2010) from wild birds with a total of 26 antigenic hemagglutinin (HA) and neuraminidase (NA) combinations. Fifteen of 16 known avian HA subtypes were isolated. Two H5N8 HPAI viruses (2016-2017) and two H5N2 LPAI viruses (2016) were isolated from wild birds and environmental samples (fresh bird feces) during surveillance before the outbreak in poultry in 2016-2017. The Ukrainian H5N1, H5N8 HPAI, and H5N2 LPAI viruses belong to different H5 phylogenetic groups. Our results demonstrate the great diversity of AI viruses in wild birds in Ukraine, as well as the importance of this region for studying the ecology of avian influenza.

KEYWORDS: Azov–Black Sea region of Ukraine; highly pathogenic and low pathogenic avian influenza virus subtype H5; surveillance; wild birds

PMID: 31713401 DOI: 10.1637/11880-042718.1

Keywords: Avian Influenza; H5N1; H5N2; H5N8; Wild Birds; Ukraine.

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A live attenuated #H5N2 prime- inactivated #H5N1 boost #vaccination induces #influenza virus #hemagglutinin #stalk specific #antibody responses (Vaccine, abstract)

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

Vaccine. 2019 Nov 7. pii: S0264-410X(19)31473-2. doi: 10.1016/j.vaccine.2019.10.084. [Epub ahead of print]

A live attenuated H5N2 prime- inactivated H5N1 boost vaccination induces influenza virus hemagglutinin stalk specific antibody responses.

Kongchanagul A1, Samnuan K2, Wirachwong P3, Surichan S3, Puthavathana P4, Pitisuttithum P5, Boonnak K6.

Author information: 1 Institute of Molecular Biosciences, Mahidol University, Thailand. 2 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Thailand. 3 Government Pharmaceutical Organization, Thailand. 4 Faculty of Medical Technology, Mahidol University, Thailand. 5 Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Thailand; Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Thailand. 6 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Thailand. Electronic address: Kobporn.boo@mahidol.ac.th.

 

Abstract

BACKGROUND:

The emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a prime-boost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies can also be induced by the prime-boost regimen.

METHOD:

Serum samples collected from 60 participants before vaccination and on days 7, 28 and 90 following boosting vaccination were used in this study. 40 participants received two doses of live attenuated H5N2 vaccine (LAIV H5N2) followed by one dose of inactivated H5N1 vaccine a year later, while 20 participants received only the inactivated H5N1 vaccine. We tested these serum samples for stalk-reactive antibodies via enzyme-linked immunosorbent (ELISA) and microneutralization assays.

RESULTS:

Stalk-specific antibody levels measured by both assays were found to be significantly higher in primed individuals than the unprimed group. ELISA results showed that 22.5, 70.5 and 57.5% of primed participants had a four-fold or more increase in stalk antibody titers on days 7, 28 and 90 following boosting vaccination, respectively; whereas the unprimed group had no increase. Peak geometric mean titers (GMT) for stalk antibodies in the LAIV H5N2 experienced group (24,675 [95% CI; 19,531-31,174]) were significantly higher than those who received only the inactivated H5N1 vaccine (8877 [7140-11,035]; p < 0·0001). Moreover, stalk antibodies displaying neutralizing activity also increased in primed participants, but not in the unprimed group.

CONCLUSION:

Our finding emphasizes the importance of prime-boost vaccination for effectively inducing stalk antibodies, which is an attractive target for developing vaccines that induce stalk reactive antibodies.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Influenza vaccine; Prime-boost vaccination; Stalk antibody

PMID: 31708176 DOI: 10.1016/j.vaccine.2019.10.084

Keywords: Avian Influenza; H5N1; H5N2; Human; Vaccines.

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Opening #Pandora’s Box at the roof of the world: #Landscape, #climate and #avian #influenza (#H5N1) (Acta Trop., abstract)

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

Acta Trop. 2019 Aug;196:93-101. doi: 10.1016/j.actatropica.2019.04.021. Epub 2019 May 4.

Opening Pandora’s Box at the roof of the world: Landscape, climate and avian influenza (H5N1).

Canavan BC1.

Author information: 1 Independent Scholar, Global Health and The Environment, 320 SE 62nd Ave., Portland, Oregon, United States. Electronic address: bcanavan@post.harvard.edu.

 

Abstract

The purpose of this case study is to examine how environmental disruption and agricultural practices act synergistically to create a perfect storm for the spread of avian influenza. Actors in this case study include the vast permafrost landscape of the Qinghai-Tibet Plateau; a wild goose that migrates over the Himalayas; the highest altitude railway in the world that traverses the plateau into Tibet; and an avian virus (H5N1). Commencing in 2001, tens of thousands of railway workers travelled to remote regions of the plateau to work on the railway. In order to feed and shelter these workers, the Chinese government established captive-bred goose farms as a source of high protein food. Beginning in 2005 and continuing in subsequent years, Qinghai Lake was the scene for the unprecedented appearance of avian influenza among migratory geese. This was a key moment in the global spread of H5N1 to poultry on three continents. Remote sensing technology suggested an ecological pathway for the transfer of avian viruses among chickens, captive-bred geese, and wild geese. Within a region experiencing rapid climate change, Qinghai Lake is warming even faster than the global average. This may relate to the persistent outbreaks of avian flu strains from Qinghai during the past twelve years. Globally, exponential increases in bird flu outbreaks are not merely a matter of chance mutations in flu viruses but also a result of antecedent social and environmental factors. The Qinghai case study provides real-world examples that bring these factors into sharp focus.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Agriculture; Avian; Climate; Influenza; Qinghai; Railway

PMID: 31063711 DOI: 10.1016/j.actatropica.2019.04.021 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N1; Panzootic; Climate change; Global warming; China.

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#Pathobiology and innate immune responses of gallinaceous #poultry to clade 2.3.4.4A #H5Nx highly pathogenic #avian #influenza virus #infection (Vet Res., abstract)

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

Vet Res. 2019 Nov 1;50(1):89. doi: 10.1186/s13567-019-0704-5.

Pathobiology and innate immune responses of gallinaceous poultry to clade 2.3.4.4A H5Nx highly pathogenic avian influenza virus infection.

Bertran K1,2, Pantin-Jackwood MJ1, Criado MF1, Lee DH1,3, Balzli CL1,4, Spackman E1, Suarez DL1, Swayne DE5.

Author information: 1 Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA, 30605, USA. 2 IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain. 3 Department of Pathobiology & Veterinary Science, University of Connecticut, Storrs, CT, 06269, USA. 4 Battelle National Biodefense Institute, National Biodefense Analysis and Countermeasures Center, 8300 Research PI, Fort Detrick, MD, 21702, USA. 5 Exotic and Emerging Avian Viral Diseases Research Unit, Southeast Poultry Research Laboratory, U.S. National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA, 30605, USA. david.swayne@usda.gov.

 

Abstract

In the 2014-2015 Eurasian lineage clade 2.3.4.4A H5 highly pathogenic avian influenza (HPAI) outbreak in the U.S., backyard flocks with minor gallinaceous poultry and large commercial poultry (chickens and turkeys) operations were affected. The pathogenesis of the first H5N8 and reassortant H5N2 clade 2.3.4.4A HPAI U.S. isolates was investigated in six gallinaceous species: chickens, Japanese quail, Bobwhite quail, Pearl guinea fowl, Chukar partridges, and Ring-necked pheasants. Both viruses caused 80-100% mortality in all species, except for H5N2 virus that caused 60% mortality in chickens. The surviving challenged birds remained uninfected based on lack of clinical disease and lack of seroconversion. Among the infected birds, chickens and Japanese quail in early clinical stages (asymptomatic and listless) lacked histopathologic findings. In contrast, birds of all species in later clinical stages (moribund and dead) had histopathologic lesions and systemic virus replication consistent with HPAI virus infection in gallinaceous poultry. These birds had widespread multifocal areas of necrosis, sometimes with heterophilic or lymphoplasmacytic inflammatory infiltrate, and viral antigen in parenchymal cells of most tissues. In general, lesions and antigen distribution were similar regardless of virus and species. However, endotheliotropism was the most striking difference among species, with only Pearl guinea fowl showing widespread replication of both viruses in endothelial cells of most tissues. The expression of IFN-γ and IL-10 in Japanese quail, and IL-6 in chickens, were up-regulated in later clinical stages compared to asymptomatic birds.

PMID: 31675983 DOI: 10.1186/s13567-019-0704-5

Keywords: Avian Influenza; H5N1; H5N2; H5N8; Reassortant strain; Poultry; Viral pathogenesis.

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#Evolution of Highly Pathogenic #Avian #Influenza A(#H5N1) Virus in #Poultry, #Togo, 2018 (Emerg Infect Dis., abstract)

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

Volume 25, Number 12—December 2019 / Dispatch

Evolution of Highly Pathogenic Avian Influenza A(H5N1) Virus in Poultry, Togo, 2018

Maxime Fusade-Boyer, Pidemnéwé S. Pato, Mathias Komlan, Koffi Dogno, Trushar Jeevan, Adam Rubrum, Casimir K. Kouakou, Emmanuel Couacy-Hymann, Daniel Batawui, Emilie Go-Maro, Pamela McKenzie, Richard J. Webby, and Mariette F. Ducatez

Author affiliations: Université de Toulouse, Toulouse, France (M. Fusade-Boyer, M.F. Ducatez); Laboratoire Central Vétérinaire de Lomé, Lomé, Togo (P.S. Pato, M. Komlan, K. Dogno, D. Batawui, E. Go-Maro); St. Jude Children’s Research Hospital, Memphis, Tennessee, USA (T. Jeevan, A. Rubrum, P. McKenzie, R.J. Webby); Central Laboratory for Animal Diseases, Bingerville, Côte d’Ivoire (C.K. Kouakou, E. Couacy-Hymann)

 

Abstract

In 2015, highly pathogenic avian influenza A(H5N1) viruses reemerged in poultry in West Africa. We describe the introduction of a reassortant clade 2.3.2.1c virus into Togo in April 2018. Our findings signal further local spread and evolution of these viruses, which could affect animal and human health.

Keywords: Avian Influenza; H5N1; Poultry; Togo.

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#Avian #Influenza A Viruses among Occupationally Exposed #Populations, #China, 2014–2016 (Emerg Infect Dis., abstract)

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

Volume 25, Number 12—December 2019 / Research

Avian Influenza A Viruses among Occupationally Exposed Populations, China, 2014–2016

Chuansong Quan1, Qianli Wang1, Jie Zhang, Min Zhao, Qigang Dai, Ting Huang, Zewu Zhang, Shenghua Mao, Yifei Nie, Jun Liu, Yun Xie, Baorong Zhang, Yuhai Bi, Weifeng Shi, Peipei Liu, Dayan Wang, Luzhao Feng, Hongjie Yu, William J. Liu  , and George F. Gao

Author affiliations: Chinese Center for Disease Control and Prevention, Beijing, China (C. Quan, J. Zhang, P. Liu, D. Wang, L. Feng, W.J. Liu, G.F. Gao); Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China (C. Quan, W. Shi); Fudan University, Shanghai, China (Q. Wang, H. Yu); Chinese Academy of Sciences, Beijing (M. Zhao, Y. Bi, G.F. Gao); Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China (Q. Dai); Sichuan Provincial Center for Disease Prevention and Control, Chengdu, China (T. Huang); Dongguan Municipal Center for Disease Control and Prevention, Dongguan, China (Z. Zhang); Shanghai Municipal Center for Disease Control and Prevention, Shanghai (S. Mao); Henan Provincial Center for Disease Control and Prevention, Zhengzhou, China (Y. Nie); Zaozhuang Center for Disease Control and Prevention, Zaozhuang, China (J. Liu); Jiangxi Provincial Center for Disease Control and Prevention, Nanchang, China (Y. Xie); Aviation General Hospital, Beijing (B. Zhang)

 

Abstract

To determine the seroprevalence and seroconversion of avian influenza virus (AIV) antibodies in poultry workers, we conducted a seroepidemiologic study in 7 areas of China during December 2014–April 2016. We used viral isolation and reverse transcription PCR to detect AIVs in specimens from live poultry markets. We analyzed 2,124 serum samples obtained from 1,407 poultry workers by using hemagglutination inhibition and microneutralization assays. We noted seroprevalence of AIV antibodies for subtypes H9N2, H7N9, H6N1, H5N1-SC29, H5N6, H5N1-SH199, and H6N6. In serum from participants with longitudinal samples, we noted seroconversion, with >4-fold rise in titers, for H9N2, H7N9, H6N1, H5N1-SC29, H6N6, H5N6, and H5N1-SH199 subtypes. We found no evidence of H10N8 subtype. The distribution of AIV antibodies provided evidence of asymptomatic infection. We correlated AIV antibody prevalence in live poultry markets with increased risk for H7N9 and H9N2 infection among poultry workers.

Keywords: Avian Influenza; Human; China; Serology; Seroprevalence; H5N1; H5N6; H6N1; H6N6; H7N9; H9N2; Live poultry Markets.

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