#Regulatory aspects of quality and safety for live #recombinant viral #vaccines against infectious diseases in #Japan (Vaccine, abstract)

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

Vaccine. 2019 Sep 7. pii: S0264-410X(19)31095-3. doi: 10.1016/j.vaccine.2019.08.031. [Epub ahead of print]

Regulatory aspects of quality and safety for live recombinant viral vaccines against infectious diseases in Japan.

Sakurai A1, Ogawa T2, Matsumoto J3, Kihira T4, Fukushima S5, Miyata I6, Shimizu H7, Itamura S8, Ouchi K9, Hamada A10, Tani K11, Okabe N12, Yamaguchi T13.

Author information: 1 Office of Vaccines and Blood Products, Pharmaceuticals and Medical Devices Agency, Shin-Kasumigaseki Bldg., 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan. Electronic address: sakurai-akira@pmda.go.jp. 2 Office of Vaccines and Blood Products, Pharmaceuticals and Medical Devices Agency, Shin-Kasumigaseki Bldg., 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan. Electronic address: ogawa-takashi@pmda.go.jp. 3 Office of Vaccines and Blood Products, Pharmaceuticals and Medical Devices Agency, Shin-Kasumigaseki Bldg., 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan. Electronic address: matsumoto-jun@pmda.go.jp. 4 Office of Vaccines and Blood Products, Pharmaceuticals and Medical Devices Agency, Shin-Kasumigaseki Bldg., 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013, Japan. Electronic address: kihira-tetsunari@pmda.go.jp. 5 Travellers’ Medical Center, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: fuku789@tokyo-med.ac.jp. 6 Department of Pediatrics, Kawasaki Medical School, 577 Matsushima, Kurashiki-Shi, Okayama 701-0192, Japan. Electronic address: miyata.kkcl@gmail.com. 7 Kawasaki City Institute for Public Health, Life Science and Environment (LiSE) Research Center 2F, 3-25-13 Tono-Machi, Kawasaki-Ku, Kawasaki-City, Kanagawa 210-0821, Japan. Electronic address: shimizu-h@city.kawasaki.jp. 8 National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-Shi, Tokyo 208-0011, Japan. Electronic address: sitamura@nih.go.jp. 9 Department of Pediatrics, Kawasaki Medical School, 577 Matsushima, Kurashiki-Shi, Okayama 701-0192, Japan. Electronic address: kouchi@med.kawasaki-m.ac.jp. 10 Travellers’ Medical Center, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: a-hamada@tokyo-med.ac.jp.  11 Project Division of ALA Advanced Medical Research, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan. Electronic address: k-tani@ims.u-tokyo.ac.jp. 12 Kawasaki City Institute for Public Health, Life Science and Environment (LiSE) Research Center 2F, 3-25-13 Tono-Machi, Kawasaki-Ku, Kawasaki-City, Kanagawa 210-0821, Japan. Electronic address: okaben-n@city.kawasaki.jp. 13 Divison of Pharmacology, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan. Electronic address: t-yamaguchi@nichiyaku.ac.jp.

 

Abstract

Recombinant viral vaccines expressing antigens of pathogenic microbes (e.g., HIV, Ebola virus, and malaria) have been designed to overcome the insufficient immune responses induced by the conventional vaccines. Our knowledge of and clinical experience with the new recombinant viral vaccines are insufficient, and a clear regulatory pathway is needed for the further development and evaluation of recombinant viral vaccines. In 2018, the research group supported by the Ministry of Health, Labour and Welfare, Japan (MHLW) published a concept paper to address the development of recombinant viral vaccines against infectious diseases. Herein we summarize the concept paper-which explains the Japanese regulatory concerns about recombinant viral vaccines-and provide a focus of discussion about the development of recombinant viral vaccines.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMID: 31506194 DOI: 10.1016/j.vaccine.2019.08.031

Keywords: Infectious Diseases; Vaccines; Japan.

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#Human-to-Human #Transmission of #Influenza A(H3N2#) Virus with Reduced Susceptibility to #Baloxavir, #Japan, February 2019 (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 11—November 2019 / Dispatch

Human-to-Human Transmission of Influenza A(H3N2) Virus with Reduced Susceptibility to Baloxavir, Japan, February 2019

Emi Takashita  , Masataka Ichikawa, Hiroko Morita, Rie Ogawa, Seiichiro Fujisaki, Masayuki Shirakura, Hideka Miura, Kazuya Nakamura, Noriko Kishida, Tomoko Kuwahara, Hiromi Sugawara, Aya Sato, Miki Akimoto, Keiko Mitamura, Takashi Abe, Masahiko Yamazaki, Shinji Watanabe, Hideki Hasegawa, and Takato Odagiri

Author affiliations: National Institute of Infectious Diseases, Tokyo, Japan (E. Takashita, H. Morita, R. Ogawa, S. Fujisaki, M. Shirakura, H. Miura, K. Nakamura, N. Kishida, T. Kuwahara, H. Sugawara, A. Sato, M. Akimoto, S. Watanabe, H. Hasegawa, T. Odagiri); Ichikawa Children’s Clinic, Kanagawa, Japan (M. Ichikawa); Eiju General Hospital, Tokyo (K. Mitamura); Abe Children’s Clinic, Kanagawa (T. Abe); Zama Children’s Clinic, Kanagawa (M. Yamazaki)

 

Abstract

In 2019, influenza A(H3N2) viruses carrying an I38T substitution in the polymerase acidic gene, which confers reduced susceptibility to baloxavir, were detected in Japan in an infant without baloxavir exposure and a baloxavir-treated sibling. These viruses’ whole-genome sequences were identical, indicating human-to-human transmission. Influenza virus isolates should be monitored for baloxavir susceptibility.

Keywords: Influenza A; H3N2; Seasonal Influenza; Antivirals; Drugs resistance; Baloxavir; Japan.

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Comparative #pathogenicity of #H5N6 subtype highly pathogenic #avian #influenza viruses in #chicken, Pekin #duck and Muscovy duck (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 May;66(3):1227-1251. doi: 10.1111/tbed.13141. Epub 2019 Feb 27.

Comparative pathogenicity of H5N6 subtype highly pathogenic avian influenza viruses in chicken, Pekin duck and Muscovy duck.

Uchida Y1, Mine J1, Takemae N1, Tanikawa T1, Tsunekuni R1, Saito T1.

Author information: 1 Influenza Unit, Division of Transboundary Animal Diseases, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), Kannondai, Tsukuba, Ibaraki, Japan.

 

Abstract

In Japan during the 2016-2017 winter season, clade 2.3.4.4 highly pathogenic avian influenza viruses (HPAIVs) of the H5N6 subtype caused 12 outbreaks in chicken and Muscovy duck farms. These viruses have been circulating in Vietnam and China since 2014. In this study, we evaluated the susceptibility of chicken, Pekin duck (Anas platyrhynchos domesticus) and Muscovy duck (Cairina moschata) to H5N6 HPAIVs that originated in Japan, Vietnam and China. The H5N6 HPAIVs examined in this study were highly lethal to chickens compared with their pathogenicity in Pekin duck and Muscovy duck. One of five chickens infected with A/Muscovy duck/Aomori/1-3T/2016 (MusDk/Aomori) survived despite viral shedding, although all of the chickens infected with the other viruses died. The 50% chicken lethal dose differed among the Japanese strains that shared the same gene constellation indicating that gene constellation was not a major determinant of pathogenicity in chicken. MusDk/Aomori, A/chicken/Niigata/1-1T/2016 (Ck/Niigata) and A/duck/Hyogo/1/2016 (Dk/Hyogo) infected all Muscovy ducks inoculated; Ck/Niigata killed 50% of the ducks it infected whereas the other two did not kill any ducks. A/chicken/Japan/AnimalQuarantine-HE144/2016 (HE144) isolated from chicken meat that originated in China was highly pathogenic to Pekin duck: all of the ducks died within 3.75 days of inoculation. This study shows that the pathogenicity of the clade 2.3.4.4 H5N6 HPAIVs differs not only between hosts but also within the same host species.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: Muscovy duck; chicken; duck; influenza virus H5N6 subtype; pathogenicity

PMID: 30720248 DOI: 10.1111/tbed.13141 [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N6; Poultry.

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A novel #H7N3 #reassortant originating from the zoonotic #H7N9 highly pathogenic #avian #influenza viruses that has adapted to #ducks (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Jul 11. doi: 10.1111/tbed.13291. [Epub ahead of print]

A novel H7N3 reassortant originating from the zoonotic H7N9 highly pathogenic avian influenza viruses that has adapted to ducks.

Nakayama M1, Uchida Y1, Shibata A2, Kobayashi Y3, Mine J1, Takemae N1, Tsunekuni R1, Tanikawa T1, Harada R2, Osaka H2, Saito T1,4.

Author information: 1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan. 2 Exotic Disease Inspection Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Tokoname, Aichi, 479-0881, Japan. 3 Pathological and Physiochemical Examination Division, Laboratory Department, Animal Quarantine Service, Ministry of Agriculture, Forestry and Fisheries, Yokohama, Kanagawa, 235-0008, Japan. 4 United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.

 

Abstract

The first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in March 2013 in China. This virus continues to circulate in poultry in China while mutating to highly pathogenic AIVs (HPAIVs). Through monitoring at airports in Japan, a novel H7N3 reassortant of the zoonotic H7N9 HPAIVs, A/duck/Japan/AQ-HE30-1/2018 (HE30-1), was detected in a poultry meat product illegally brought by a passenger from China into Japan. We analyzed the genetic, pathogenic, and antigenic characteristics of HE30-1 by comparing it with previous zoonotic H7N9 AIVs and their reassortants. Phylogenetic analysis of the entire HE30-1 genomic sequence revealed that it comprised at least three different sources; the HA (H7), PB1, PA, NP, M, and NS segments of HE30-1 were directly derived from H7N9 AIVs, whereas the NA (N3) and PB2 segments of HE30-1 were unrelated to zoonotic H7N9. Experimental infection revealed that HE30-1 was lethal in chickens but not in domestic or mallard ducks. HE30-1 was shed from and replicated in domestic and mallard ducks and chickens, whereas previous zoonotic H7N9 AIVs have not adapted well to ducks. This finding suggests the possibility that HE30-1 may disseminate to remote area by wild bird migration once it establishes in wild bird population. A hemagglutination-inhibition assay indicated that antigenic drift has occurred among the reassortants of zoonotic H7N9 AIVs; HE30-1 showed similar antigenicity to some of those H7N9 AIVs, suggesting it might be prevented by the H5/H7 inactivated vaccine that was introduced in China in 2017. Our study reports the emergence of a new reassortant of zoonotic H7N9 AIVs with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.

This article is protected by copyright. All rights reserved.

KEYWORDS: adaptation to ducks; animal experiments; novel H7N3 reassortant; zoonotic H7N9 avian influenza viruses

PMID: 31293102 DOI: 10.1111/tbed.13291

Keywords: Avian Influenza; H7N3; H7N9; Reassortant strain; Animal models.

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Acute #ischemic #colitis with hematochezia related to #baloxavir marboxil #treatment for #influenza A (J Infect Chemother., abstract)

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

J Infect Chemother. 2019 Jun 5. pii: S1341-321X(19)30141-2. doi: 10.1016/j.jiac.2019.05.009. [Epub ahead of print]

Acute ischemic colitis with hematochezia related to baloxavir marboxil treatment for influenza A.

Kanai N1, Hashimoto T2, Fukuda M3, Shijyo T4.

Author information: 1 Niiza Hospital, Department of Pharmacy, 3-14-30, Horinouchi, Niiza, Saitama, 352-0023, Japan. Electronic address: n8_kanai@yahoo.co.jp. 2 Niiza Hospital, Department of Pharmacy, 3-14-30, Horinouchi, Niiza, Saitama, 352-0023, Japan. Electronic address: h.taka@zb.cyberhome.ne.jp. 3 Niiza Hospital, Department of Internal Medicine, 3-14-30, Horinouchi, Niiza, Saitama, 352-0023, Japan. Electronic address: m_fukuda02@tmg.or.jp. 4 Niiza Hospital, Department of Gastroenterological Surgery, 3-14-30, Horinouchi, Niiza, Saitama, 352-0023, Japan. Electronic address: tsj5255md@yahoo.co.jp.

 

Abstract

Oseltamivir, an established oral anti-influenza medication, increases the risk of ischemic colitis. Baloxavir marboxil is a novel oral anti-influenza medication, and few studies have evaluated its potential side effects, including ischemic colitis. Moreover, as influenza A can also induce ischemic colitis, drug-induced colitis associated with anti-influenza medication is not clearly understood. In this report, we describe the case of a 62-year-old Japanese woman who developed acute ischemic colitis after taking baloxavir for influenza A. The day after taking baloxavir (day 2), the patient experienced abdominal pain, diarrhea, and nausea. On day 3, she had developed hematochezia and decided to visit our hospital. Upon presentation, inflammation of the descending and sigmoid colon was detected by abdominal echography and computed tomography. Fluid replacement therapy and dietary restrictions were initiated. On day 4, the inflammation of the descending colon and marked intestinal edema were confirmed by colonoscopy. She was clinically diagnosed with ischemic colitis, from which she recovered completely by day 9. This case suggests that patients taking baloxavir may be at risk of developing ischemic colitis with hematochezia and underscores the need to further study the induction of this condition by commonly used oral anti-influenza agents.

Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: Acute ischemic colitis; Baloxavir marboxil; Hematochezia; Influenza A

PMID: 31176533 DOI: 10.1016/j.jiac.2019.05.009

Keywords: Antivirals; Drugs Safety; Seasonal Influenza; Baloxavir marboxil.

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In vitro #neuraminidase inhibitory concentration (#IC50) of four neuraminidase inhibitors in the #Japanese 2017-18 #season: Comparison with the 2010-11 to 2016-17 seasons (J Infect Chemother., abstract)

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

J Infect Chemother. 2019 May 14. pii: S1341-321X(19)30099-6. doi: 10.1016/j.jiac.2019.04.007. [Epub ahead of print]

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2017-18 season: Comparison with the 2010-11 to 2016-17 seasons.

Ikematsu H1, Kawai N2, Chong Y3, Bando T2, Iwaki N2, Kashiwagi S2.

Author information: 1 Japan Physicians Association, Tokyo, Japan; Ricerca Clinica Co., Fukuoka, Japan. Electronic address: ikematsu@gray.plala.or.jp. 2 Japan Physicians Association, Tokyo, Japan. 3 Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

 

Abstract

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) of the viruses epidemic in the 2017-18 Japanese influenza season, we measured the 50% inhibitory concentration (IC50) for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2016-17 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 237 virus isolates, 50 A(H1N1)pdm09, 92 A(H3N2), and 95 B were measured. No A(H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2017-18 season. No isolates with highly reduced sensitivity to the four NAIs have been found for A(H3N2) or B from the 2010-11 to 2017-18 seasons. The geometric mean IC50s of the four NAIs were quite consistent during the eight studied seasons. These results indicate that the sensitivity to the four commonly used NAIs has been maintained.

Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: 50% inhibitory concentration; Influenza virus; Neuraminidase inhibitor; Resistance; Surveillance

PMID: 31101530 DOI: 10.1016/j.jiac.2019.04.007

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Japan; Seasonal Influenza; H1N1pdm09; H3N2; Influenza B.

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#Genetics and #pathogenicity of #H5N6 highly pathogenic #avian #influenza viruses isolated from #wildbirds and a #chicken in #Japan during winter 2017-2018 (Virology, abstract)

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

Virology. 2019 May 2;533:1-11. doi: 10.1016/j.virol.2019.04.011. [Epub ahead of print]

Genetics and pathogenicity of H5N6 highly pathogenic avian influenza viruses isolated from wild birds and a chicken in Japan during winter 2017-2018.

Mine J1, Uchida Y1, Nakayama M1, Tanikawa T1, Tsunekuni R1, Sharshov K2, Takemae N1, Sobolev I2, Shestpalov A2, Saito T3.

Author information: 1 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan; Thailand-Japan Zoonotic Diseases Collaboration Center, Kasetklang, Chatuchak, Bangkok, 10900, Thailand. 2 Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia. 3 Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki, 305-0856, Japan; Thailand-Japan Zoonotic Diseases Collaboration Center, Kasetklang, Chatuchak, Bangkok, 10900, Thailand; United Graduate School of Veterinary Sciences, Gifu University, 1-1, Yanagito, Gifu, Gifu, 501-1112, Japan. Electronic address: taksaito@affrc.go.jp.

 

Abstract

An H5N6 highly pathogenic avian influenza virus (HPAIV) outbreak occurred in poultry in Japan during January 2018, and H5N6 HPAIVs killed several wild birds in 3 prefectures during Winter 2017-2018. Time-measured phylogenetic analyses demonstrated that the Hemagglutinin (HA) and internal genes of these isolates were genetically similar to clade 2.3.4.4.B H5N8 HPAIVs in Europe during Winter 2016-2017, and Neuraminidase (NA) genes of the poultry and wild bird isolates were gained through distinct reassortments with AIVs that were estimated to have circulated possibly in Siberia during Summer 2017 and Summer 2016, respectively. Lethal infectious dose to chickens was similar between the poultry and wild-bird isolates. H5N6 HPAIVs during Winter 2017-2018 in Japan had higher 50% chicken lethal doses and lower transmission efficiency than the H5Nx HPAIVs that caused previous outbreaks in Japan, thus explaining in part why cases during the 2017-2018 outbreak were sporadic.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Animal RNA virus; H5N6 highly pathogenic avian influenza; Pathogenicity; Phylogeny

PMID: 31071540 DOI: 10.1016/j.virol.2019.04.011

Keywords: Avian Influenza; H5N6; H5N8; Wild Birds; Poultry; Japan.

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