Repeated #vaccination against matched #H3N2 #influenza virus gives less #protection than single vaccination in ferrets (npj Vaccines, abstract)

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

Article | OPEN | Published: 09 July 2019

Repeated vaccination against matched H3N2 influenza virus gives less protection than single vaccination in ferrets

Nedzad Music, Wen-Pin Tzeng, F. Liaini Gross, Min Z. Levine, Xiyan Xu, Wun-Ju Shieh, Terrence M. Tumpey, Jacqueline M. Katz & Ian A. York

npj Vaccines, volume 4, Article number: 28 (2019)



Epidemiological studies suggest that humans who receive repeated annual immunization with influenza vaccine are less well protected against influenza than those who receive vaccine in the current season only. To better understand potential mechanisms underlying these observations, we vaccinated influenza-naive ferrets either twice, 10 months apart (repeated vaccination group; RV), or once (current season only group; CS), using a prime-boost regimen, and then challenged the ferrets with A/Hong Kong/4801/2014(H3N2). Ferrets that received either vaccine regimen were protected against influenza disease and infection relative to naive unvaccinated ferrets, but the RV group shed more virus, especially at the peak of virus shedding 2 days post infection (p < 0.001) and regained weight more slowly (p < 0.05) than those in the CS group. Qualitative, rather than quantitative, differences in the antibody response may affect protection after repeated influenza vaccination.

Keywords: Seasonal Influenza; H3N2; Vaccines; Animal models.



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)



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.


The effect of #influenza #vaccination #history on changes in #hemagglutination #inhibition #titers following receipt of the 2015/16 influenza #vaccine in older #adults in #HK (J Infect Dis., abstract)

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

The effect of influenza vaccination history on changes in hemagglutination inhibition titers following receipt of the 2015/16 influenza vaccine in older adults in Hong Kong

Tiffany W Y Ng, Ranawaka A P M Perera, Vicky J Fang, Emily M Yau, J S Malik Peiris, Yat Hung Tam, Benjamin J Cowling

The Journal of Infectious Diseases, jiz327,

Published: 06 July 2019




Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same.


An observational study was conducted among 827 older adults aged ≥75 years in Hong Kong. Sera were collected immediately before and one month after receipt of the 2015/16 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay, and compared mean fold rise in titers from pre- to post-vaccination, and the proportion with post-vaccination titers ≥40 and ≥160.


Participants who reported receipt of vaccination during either of the previous two years had lower mean fold rise against all strains compared to those who were not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak following repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportion of participants with post-vaccination titers ≥40 and ≥160.


Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.

influenza vaccine, repeated vaccination, immune response

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:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Seasonal Influenza; H3N2; Vaccines; HK.


A case of #reassortant seasonal #influenza A(#H1N2) virus, #Denmark, April 2019 (Euro Surveill., abstract)

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

A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019

Ramona Trebbien1, Anders Koch2, Lene Nielsen3, Dår Kristian Kur4, Pontus Westerström5, Tyra Grove Krause2

Affiliations: 1 National Influenza Center, Statens Serum Institut, Copenhagen, Denmark; 2 Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark; 3 Department of Clinical Microbiology, Herlev Hospital, Copenhagen University, Herlev, Denmark; 4 Department of Clinical Biochemistry, North Zealand Hospital, Hillerød, Denmark; 5 Department of Pulmonary and Infectious Diseases, North Zealand Hospital, Hillerød, Denmark

Correspondence:  Ramona Trebbien

Citation style for this article: Trebbien Ramona, Koch Anders, Nielsen Lene, Kur Dår Kristian, Westerström Pontus, Krause Tyra Grove. A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019. Euro Surveill. 2019;24(27):pii=1900406.

Received: 21 Jun 2019;   Accepted: 03 Jul 2019



A reassortant influenza A subtype H1N2 virus with gene segments from seasonal A(H1N1)pdm09 virus (HA, MP, NP, NS, PA, PB1 and PB2) and seasonal A(H3N2) virus (NA) was identified in a routine surveillance sample in Denmark. The patient recovered fully. This is the second reassortant influenza A(H1N2) virus identified in Europe in the 2018/19 influenza season, with the first case being detected December 2018 in Sweden.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; H1N2; Reassortant strain; Human; Denmark.


A rare case of #influenza A (#H3N2)-associated #encephalitis with #seizure (Am J Emerg Med., abstract)

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

Am J Emerg Med. 2019 Jun 16. pii: S0735-6757(19)30406-1. doi: 10.1016/j.ajem.2019.06.027. [Epub ahead of print]

A rare case of influenza A (H3N2)-associated encephalitis with seizure.

Yuan HT1, Ho TH2, Lee JT2, Chen PC3, Wang CW4, Yang FC5.

Author information: 1 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan; Division of Neurology, Department of Internal Medicine, Tri-Service General Hospital Sungsan Branch, National Defense Medical Center, No.131, Jiankang Road, Songshan 104, Taipei, Taiwan. 2 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 3 Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 4 Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. 5 Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan. Electronic address:



Influenza-associated acute encephalopathy (IAE) is more prevalent in children than in adults and often results in neurological sequelae or even death. Diagnosis of IAE is difficult as clinical presentation varies significantly and the influenza virus is rarely detected in cerebrospinal fluid. Moreover, seizures in adults due to influenza infection are rare. Herein, we describe the case of an adult presenting with both acute encephalitis and seizures. A 38-year-old female was admitted to the emergency department with acute respiratory symptoms and fever, followed by quick progression to stupor within 24 h. A rapid antigen test was influenza A-positive, and polymerase chain reaction of nasal secretions confirmed the H3N2 subtype. Brain magnetic resonance imaging showed bilateral water restriction lesions at the thalamus and the cerebellum and an electroencephalogram showed frequent episodic generalized sharp-and-slow waves over the bilateral frontal region. Based on the neuroimaging and laboratory findings, we diagnosed the patient with adult influenza A (H3N2)-related encephalitis complicated by seizure. Treatment with oseltamivir and anticonvulsants led to complete neurologic recovery by day 14. This report describes two unusual neurological manifestations of influenza A, i.e., encephalitis and seizures, in an adult. We emphasize that, in adults presenting with acute viral encephalitis, clinicians should consider influenza infection as part of the differential diagnosis, and that typical neuroimaging in conjunction with laboratory detection of influenza virus and/or intrathecal antibody production suggestive of IAE, may help establish an accurate diagnosis.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: Adult; H3N2; Influenza A; Influenza associated encephalitis; Influenza associated seizures in adults; Magnetic resonance imaging

PMID: 31230923 DOI: 10.1016/j.ajem.2019.06.027

Keywords: Seasonal Influenza; H3N2; Encephalitis.


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



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

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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.


#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,, 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:



  • 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.



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.