Susceptibility of #Influenza A, B, C, and D Viruses to #Baloxavir (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 10—October 2019 / Dispatch

Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir

Vasiliy P. Mishin, Mira C. Patel, Anton Chesnokov, Juan De La Cruz, Ha T. Nguyen, Lori Lollis, Erin Hodges, Yunho Jang, John Barnes, Timothy Uyeki, Charles T. Davis, David E. Wentworth, and Larisa V. Gubareva

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (V.P. Mishin, M.C. Patel, A. Chesnokov, J. De La Cruz, H.T. Nguyen, L. Lollis, E. Hodges, Y. Jang, J. Barnes, T. Uyeki, C.T. Davis, D.E. Wentworth, L.V. Gubareva); Battelle Memorial Institute, Atlanta (M.C. Patel, J. De La Cruz, H.T. Nguyen, L. Lollis)

 

Abstract

Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2–98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Favipiravir; Baloxavir; Influenza A; Influenza B; Influenza C; Influenza D; H1N1pdm09; H3N2; H7N9.

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#Update: #Influenza #Activity in the #USA During the 2018–19 Season and Composition of the 2019–20 Influenza #Vaccine (MMWR Morb Mortal Wkly Rep., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), MMWR Morbidity and Mortality Weekly Report, full page: (LINK). Abstract, edited.]

Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine

Weekly / June 21, 2019 / 68(24);544–551

Xiyan Xu, MD1; Lenee Blanton, MPH1; Anwar Isa Abd Elal1; Noreen Alabi, MPH1; John Barnes, PhD1; Matthew Biggerstaff, ScD1; Lynnette Brammer, MPH1; Alicia P. Budd, MPH1; Erin Burns, MA1; Charisse N. Cummings, MPH1; Shikha Garg, MD1; Rebecca Kondor, PhD1; Larisa Gubareva, PhD1; Krista Kniss, MPH1; Sankan Nyanseor, MPH1; Alissa O’Halloran, MSPH1; Melissa Rolfes, PhD1; Wendy Sessions, MPH1; Vivien G. Dugan, PhD1; Alicia M. Fry, MD1; David E. Wentworth, PhD1; James Stevens, PhD1; Daniel Jernigan, MD1

Corresponding author: Xiyan Xu, XXu@cdc.gov, 404-639-1657.

{1} Influenza Division, National Center for Immunization and Respiratory Diseases, CDC.

All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Suggested citation for this article: Xu X, Blanton L, Elal AI, et al. Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine. MMWR Morb Mortal Wkly Rep 2019;68:544–551. DOI: http://dx.doi.org/10.15585/mmwr.mm6824a3

 

Summary

  • What is already known about this topic?
    • CDC collects, compiles, and analyzes data on influenza activity and viruses in the United States.
  • What is added by this report?
    • The 2018–19 influenza season was a moderate severity season with two waves of influenza A activity of similar magnitude during the season: A(H1N1)pdm09 predominated from October 2018 to mid-February 2019, and A(H3N2) activity increased from mid-February through mid-May.
  • What are the implications for public health practice?
    • Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.
    • Testing for seasonal influenza viruses and monitoring for emergence of antigenic drift variant viruses should continue year-round.

 

Abstract

Influenza activity* in the United States during the 2018–19 season (September 30, 2018–May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017–18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Keywords: Seasonal Influenza; USA; Vaccines; Antivirals; Oseltamivir; Zanamivir; Baloxavir marboxil.

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Development of #Influenza B #Universal #Vaccine Candidates Using the “Mosaic” Hemagglutinin Approach (J Virol., abstract)

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

Development of Influenza B Universal Vaccine Candidates Using the “Mosaic” Hemagglutinin Approach

Weina Sun, Ericka Kirkpatrick, Megan Ermler, Raffael Nachbagauer, Felix Broecker, Florian Krammer, Peter Palese

Terence S. Dermody, Editor

DOI: 10.1128/JVI.00333-19

 

ABSTRACT

Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on “mosaic” hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B hemagglutinin with corresponding sequences from exotic influenza A hemagglutinins and expressed them as soluble trimeric proteins. Sequential vaccination with recombinant mosaic B hemagglutinin proteins conferred cross-protection against both homologous and heterologous influenza B virus strains in the mouse model. Of note, we rescued recombinant influenza B viruses expressing mosaic B hemagglutinins, which could serve as the basis for a universal influenza B virus vaccine.

 

IMPORTANCE

This work reports a universal influenza B virus vaccination strategy based on focusing antibody responses to conserved head and stalk epitopes of the hemagglutinin. Recombinant mosaic influenza B hemagglutinin proteins and recombinant viruses have been generated as novel vaccine candidates. This vaccine strategy provided broad cross-protection in the mouse model. Our findings will inform and drive development toward a more effective influenza B virus vaccine.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Seasonal Influenza; Influenza B; Vaccines; Animal models.

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#Mucosal #Immunity against #Neuraminidase Prevents #Influenza B Virus #Transmission in Guinea Pigs (mBio, abstract)

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

Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

Meagan McMahon, Ericka Kirkpatrick, Daniel Stadlbauer, Shirin Strohmeier, Nicole M. Bouvier, Florian Krammer

Stacey Schultz-Cherry, Editor

DOI: 10.1128/mBio.00560-19

 

ABSTRACT

Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses.

 

IMPORTANCE

Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.

Keywords: Seasonal Influenza; Influenza B; Vaccines; Animal models.

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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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#Dual and #triple #infections with #Influenza A and B viruses: a case-control study in Southern #Brazil (J Infect Dis., abstract)

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

Dual and triple infections with Influenza A and B viruses: a case-control study in Southern Brazil

Tatiana Schäffer Gregianini, Ivana R Santos Varella, Patricia Fisch, Letícia Garay Martins, Ana B G Veiga

The Journal of Infectious Diseases, jiz221, https://doi.org/10.1093/infdis/jiz221

Published: 29 April 2019

 

Abstract

Influenza surveillance is important for disease control and should consider possible coinfection with different viruses, which can be associated with disease severity. This study analyzed 34,459 patients with respiratory infection from 2009 to 2018, of which 8,011 were positive for IAV or IBV. We found 18 cases of influenza dual infection, including H1N1pdm09 and H3N2 (1 case), H1N1pdm09 and IBV (6 cases), H3N2 and IBV (8 cases), and non-subtyped IAV and IBV (3 cases); and one case of triple detection of H3N2, H1N1pdm09 and IBV. Compared with mono-infected patients (n=76), coinfection was significantly associated with cardiopathy and death. Besides demographics and clinical symptoms, we assessed vaccination status, antiviral treatment, time of antiviral use, hospitalization, and ICU admission, but no significant differences were found between coinfected or mono-infected cases. Our findings indicate that influenza coinfection occurs more often than previously reported and that it can lead to a worse disease outcome.

Influenza Virus, Coinfection, Respiratory Infections

Topic: influenza – heart diseases – antiviral agents – brazil – demography – herpesvirus 1, cercopithecine – infectious mononucleosis – intensive care unit – orthomyxoviridae – respiratory tract infections – vaccination – infection – influenzavirus a – viruses – coinfection – surveillance, medical – influenza a virus, h3n2 subtype – severity of illness

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. 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: Seasonal Influenza; H1N1pdm09; H3N2; Influenza B; Brazil.

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Development of #Influenza B #Universal #Vaccine Candidates using the “#Mosaic” #Hemagglutinin Approach (J Virol., abstract)

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

Development of Influenza B Universal Vaccine Candidates using the “Mosaic” Hemagglutinin Approach

Weina Sun, Ericka Kirkpatrick, Megan Ermler, Raffael Nachbagauer, Felix Broecker, Florian Krammer, Peter Palese

DOI: 10.1128/JVI.00333-19

 

ABSTRACT

Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on mosaic hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B hemagglutinin with corresponding sequences from exotic influenza A hemagglutinins and expressed them as soluble trimeric proteins. Sequential vaccination with recombinant mosaic B hemagglutinin proteins conferred cross-protection against both homologous and heterologous influenza B virus strains in the mouse model. Of note, we rescued recombinant influenza B viruses expressing mosaic B hemagglutinins, which could serve as the basis for a universal influenza B virus vaccine.

 

IMPORTANCE

This work reports a universal influenza B virus vaccination strategy based on focusing antibody responses to conserved head and stalk epitopes of the hemagglutinin. Recombinant mosaic influenza B hemagglutinin proteins and recombinant viruses have been generated as novel vaccine candidates. This vaccine strategy provided broad cross-protection in the mouse model. Our findings will inform and drive the development toward a more effective influenza B virus vaccine.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Seasonal Influenza; Influenza B; Vaccines.

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