Recalling the #Future: #Immunological #Memory Toward Unpredictable #Influenza Viruses (Front Immunol., abstract)

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

Front Immunol. 2019 Jul 2;10:1400. doi: 10.3389/fimmu.2019.01400. eCollection 2019.

Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses.

Auladell M1, Jia X1, Hensen L1, Chua B1,2, Fox A3, Nguyen THO1, Doherty PC1,4, Kedzierska K1.

Author information: 1 Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia. 2 Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan. 3 WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 4 Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, United States.



Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing memory B cell and T cell pools is thus the key for maintaining protective immunity to seasonal, pandemic and avian influenza viruses. Long-lived antibody secreting cells (ASCs) are responsible for maintaining antibody levels in peripheral blood. Generated with CD4+ T help after naïve B cell precursors encounter their cognate antigen, the linked processes of differentiation (including Ig class switching) and proliferation also give rise to memory B cells, which then can change rapidly to ASC status after subsequent influenza encounters. Given that influenza viruses evolve rapidly as a consequence of antibody-driven mutational change (antigenic drift), the current influenza vaccines need to be reformulated frequently and annual vaccination is recommended. Without that process of regular renewal, they provide little protection against “drifted” (particularly H3N2) variants and are mainly ineffective when a novel pandemic (2009 A/H1N1 “swine” flu) strain suddenly emerges. Such limitation of antibody-mediated protection might be circumvented, at least in part, by adding a novel vaccine component that promotes cross-reactive CD8+ T cells specific for conserved viral peptides, presented by widely distributed HLA types. Such “memory” cytotoxic T lymphocytes (CTLs) can rapidly be recalled to CTL effector status. Here, we review how B cells and follicular T cells are elicited following influenza vaccination and how they survive into a long-term memory. We describe how CD8+ CTL memory is established following influenza virus infection, and how a robust CTL recall response can lead to more rapid virus elimination by destroying virus-infected cells, and recovery. Exploiting long-term, cross-reactive CTL against the continuously evolving and unpredictable influenza viruses provides a possible mechanism for preventing a disastrous pandemic comparable to the 1918-1919 H1N1 “Spanish flu,” which killed more than 50 million people worldwide.

KEYWORDS: B cells; T cells; immunological memory; influenza; vaccine

PMID: 31312199 PMCID: PMC6614380 DOI: 10.3389/fimmu.2019.01400

Keywords: Influenza A; Seasonal Influenza; Pandemic Influenza; Vaccines; Immunology.



#NAIs and #Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine #Treatment Effectiveness Among Patients Hospitalized With Nonfatal #H1N1pdm09 Virus Infection (J Infect Dis., abstract)

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

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

Sudhir Venkatesan, Puja R Myles, Kirsty J Bolton, Stella G Muthuri, Tarig Al Khuwaitir, Ashish P Anovadiya, Eduardo Azziz-Baumgartner, Tahar Bajjou, Matteo Bassetti, Bojana Beovic, Barbara Bertisch, Isabelle Bonmarin, Robert Booy, Victor H Borja-Aburto, Heinz Burgmann, Bin Cao, Jordi Carratala, Tserendorj Chinbayar, Catia Cilloniz, Justin T Denholm, Samuel R Dominguez, Pericles A D Duarte, Gal Dubnov-Raz, Sergio Fanella, Zhancheng Gao, Patrick Gérardin, Maddalena Giannella, Sophie Gubbels, Jethro Herberg Anjarath, Lorena Higuera Iglesias, Peter H Hoeger, Xiao Yun Hu, Quazi T Islam, Mirela F Jiménez, Gerben Keijzers, Hossein Khalili, Gabriela Kusznierz, Ilija Kuzman, Eduard Langenegger, Kamran B Lankarani, Yee-Sin Leo, Romina P Libster, Rita Linko, Faris Madanat, Efstratios Maltezos, Abdullah Mamun, Toshie Manabe, Gokhan Metan, Auksė Mickiene, Dragan Mikić, Kristin G I Mohn, Maria E Oliva, Mehpare Ozkan Dhruv, Parekh Mical, Paul Barbara A Rath, Samir Refaey, Alejandro H Rodríguez, Bunyamin Sertogullarindan, Joanna Skręt-Magierło, Ayper Somer, Ewa Talarek, Julian W Tang, Kelvin To Dat Tran, Timothy M Uyeki, Wendy Vaudry, Tjasa Vidmar, Paul Zarogoulidis, PRIDE Consortium Investigators, Jonathan S Nguyen-Van-Tam

The Journal of Infectious Diseases, jiz152,

Published: 17 July 2019




The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear.


We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded.


We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78–.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS.


When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Neuraminidase inhibitors, pandemic influenza, IPD meta-analysis, length of stay, antivirals

Issue Section: Major Article

Keywords: Seasonal Influenza; H1N1pdm09; Antivirals; Oseltamivir.


#Neuraminidase expressing #VLP #vaccine provides effective cross #protection against #influenza virus (Virology, abstract)

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

Virology. 2019 Jul 8;535:179-188. doi: 10.1016/j.virol.2019.07.008. [Epub ahead of print]

Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus.

Kim KH1, Lee YT1, Park S1, Jung YJ1, Lee Y1, Ko EJ1, Kim YJ1, Li X2, Kang SM3.

Author information: 1 Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA. 2 Center for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFP, Health Canada, Ottawa, ON, Canada. 3 Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, USA. Electronic address:



Neuraminidase is the second major surface antigen on influenza virus. We investigated the immunogenicity and cross protective efficacy of virus-like particle containing neuraminidase derived from 2009 pandemic H1N1 influenza virus (N1 VLP) in comparison with inactivated split influenza vaccine. Immunization of mice with N1 VLP induced antibody responses specific for virus and cross-reactive neuraminidase inhibition activity whereas an inactivated split vaccine induced strain-specific hemagglutination inhibition activity. N1 VLP-immunized mice developed cross protective immunity against antigenically different influenza viruses, as determined by body weight changes, lung viral titers, infiltrating innate immune cells, and cytokines, and antibody secreting cells, and germinal center B cells. Also, N1 VLP-immune sera provided cross-protection in naïve mice. Immunity by N1 VLP vaccination was not compromised in Fc receptor γ-chain deficient mice. These results suggest that neuraminidase-presenting VLP can be developed as an effective cross-protective vaccine candidate along with current influenza vaccination.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

KEYWORDS: Cross protection; Influenza virus; Neuraminidase vaccine; Virus-like particle

PMID: 31310875 DOI: 10.1016/j.virol.2019.07.008

Keywords: Seasonal Influenza; Vaccines.


#Baloxavir and #Treatment-Emergent #Resistance: #PublicHealth Insights and Next Steps (J Infect Dis., summary)

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

Baloxavir and Treatment-Emergent Resistance: Public Health Insights and Next Steps

Larisa V Gubareva, Alicia M Fry

The Journal of Infectious Diseases, jiz245,

Published: 16 July 2019

Issue Section: Editorial Commentary



Drug resistance is a topic of significant concern in the treatment of infectious diseases caused by rapidly evolving RNA viruses that can persist (eg, human immunodeficiency virus and hepatitis C virus) or reinfect (eg, influenza virus). Combination drug therapy is standard of care for the treatment of infections by rapidly mutating RNA viruses [1, 2]. However, it is not a common approach for treating influenza virus infections, partly because of the limited number of anti-influenza drugs and drug targets. We now know that all of the classes of anti-influenza drugs—M2 blockers, neuraminidase inhibitors (NAIs), and the newly licensed cap-dependent endonuclease inhibitor (baloxavir marboxil)—have low genetic barriers to resistance: 1 or 2 amino acid substitutions are sufficient to gain resistance [3, 4].





The statements and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Financial support.

This work was supported by the Centers for Disease Control and Prevention.

Potential conflicts of interest.

Both authors: No reported conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Baloxavir; Seasonal Influenza.


#Influenza-associated #pneumonia hospitalizations in #Uganda, 2013-2016 (PLoS One, abstract)

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


Influenza-associated pneumonia hospitalizations in Uganda, 2013-2016

Gideon O. Emukule , Barbara Namagambo, Nicholas Owor, Barnabas Bakamutumaho, John T. Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Stefano Tempia, Sandra S. Chaves, Julius J. Lutwama

Published: July 15, 2019 / DOI:




Influenza is an important contributor to acute respiratory illness, including pneumonia, and results in substantial morbidity and mortality globally. Understanding the local burden of influenza-associated severe disease can inform decisions on allocation of resources toward influenza control programs. Currently, there is no national influenza vaccination program in Uganda.


In this study, we used data on pneumonia hospitalizations that were collected and reported through the Health Management Information System (HMIS) of the Ministry of Health, Uganda, and the laboratory-confirmed influenza positivity data from severe acute respiratory illness (SARI) surveillance in three districts (Wakiso, Mbarara, and Tororo) to estimate the age-specific incidence of influenza-associated pneumonia hospitalizations from January 2013 through December 2016.


The overall estimated mean annual rate of pneumonia hospitalizations in the three districts was 371 (95% confidence interval [CI] 323–434) per 100,000 persons, and was highest among children aged <5 years (1,524 [95% CI 1,286–1,849]) compared to persons aged ≥5 years (123 [95% CI 105–144]) per 100,000 persons. The estimated mean annual rate of influenza-associated pneumonia hospitalization was 34 (95% CI 23–48) per 100,000 persons (116 [95% CI 78–165] and 16 [95% CI 6–28] per 100,000 persons among children aged <5 years and those ≥5 years, respectively). Among children aged <5 years, the rate of hospitalized influenza-associated pneumonia was highest among those who were <2 years old (178 [95% CI 109–265] per 100,000 persons). Over the period of analysis, the estimated mean annual number of hospitalized influenza-associated pneumonia cases in the three districts ranged between 672 and 1,436, of which over 70% represent children aged <5 years.


The burden of influenza-associated pneumonia hospitalizations was substantial in Uganda, and was highest among young children aged <5 years. Influenza vaccination may be considered, especially for very young children.


Citation: Emukule GO, Namagambo B, Owor N, Bakamutumaho B, Kayiwa JT, Namulondo J, et al. (2019) Influenza-associated pneumonia hospitalizations in Uganda, 2013-2016. PLoS ONE 14(7): e0219012.

Editor: Ray Borrow, Public Health England, UNITED KINGDOM

Received: February 7, 2019; Accepted: June 13, 2019; Published: July 15, 2019

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All relevant data are within the manuscript and its Supporting Information files. However, should there be need for additional data, a request can be made directly to Dr. Julius Lutwama (Program Coordinator, and Head of the Department of Arbovirology and Emerging Viral Infections at Uganda Virus Research Institute, Uganda; Email:

Funding: This study was supported by U.S. Centers for Disease Control and Prevention. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Seasonal Influenza; Pneumonia; SARI; Uganda.


#Effectiveness of partial and full #influenza #vaccination in #children aged <9 years in #HK, 2011-2019 (J Infect Dis., abstract)

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

Effectiveness of partial and full influenza vaccination in children aged <9 years in Hong Kong, 2011-2019

Huiying Chua, Susan S Chiu, Eunice L Y Chan, Shuo Feng, Mike Y W Kwan, Joshua S C Wong, J S Malik Peiris, Benjamin J Cowling

The Journal of Infectious Diseases, jiz361,

Published: 09 July 2019




Two doses of influenza vaccination are recommended for previously unvaccinated children aged <9 years, and receipt of one dose is sometimes termed “partial vaccination”. We assessed the vaccine effectiveness (VE) against influenza hospitalization of partial and full influenza vaccination among children in Hong Kong.


Using the test-negative design we enrolled 23,187 children aged <9 years admitted to hospitals with acute respiratory illness between September 2011 through to March 2019. Vaccination and influenza status were recorded. Fully vaccinated children included those vaccinated with two doses, or one dose if they were previously vaccinated. Partially vaccinated children included those who should receive two doses but received only one dose. We estimated VE using conditional logistic regression models matching on epidemiological week.


Overall VE estimates among fully and partially vaccinated children were 73% (95% confidence interval, CI: 69% ,77%) and 31% (95% CI: 8%, 48%), respectively. Consistently higher VE was observed in fully vaccinated children against each influenza type/subtype. VE of partial vaccination did not vary by age groups.


Partial vaccination was significantly less effective than full vaccination. Our study supports the current recommendation of two doses of influenza vaccination in previously unvaccinated children <9 years of age.

Topic: influenza – child – hong kong – influenza vaccines – respiratory tract infections – vaccination – vaccines – single-dose regimen

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; Vaccines; HK PRC SAR.


Effect of #age on relative #effectiveness of high-dose versus standard-dose #influenza #vaccines among #US #Medicare beneficiaries ages 65 years and older (J Infect Dis., abstract)

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

Effect of age on relative effectiveness of high-dose versus standard-dose influenza vaccines among US Medicare beneficiaries ages 65 years and older

Yun Lu, PhD, Yoganand Chillarige, MPA, Hector S Izurieta, MD, Yuqin Wei, MS, Wenjie Xu, BA, Michael Lu, BS, Heng-Ming Sung, MPH, Arnstein Lindaas, MA, Michael Wernecke, BS, Thomas MaCurdy, PhD, Jeffrey Kelman, MD, Richard A Forshee, PhD

The Journal of Infectious Diseases, jiz360,

Published: 09 July 2019




Studies have found that the high-dose influenza vaccine has higher relative vaccine effectiveness (RVE) compared to standard-dose vaccines in some seasons. We evaluated the effect of age on the high-dose versus standard-dose RVE among Medicare beneficiaries.


A six-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries ages ≥65 years. Poisson regression was used to evaluate the effect of age on high-dose versus standard-dose RVE in preventing influenza hospitalizations.


The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza hospital encounters (influenza inpatient stays and emergency department visits) in the 2012–13 (RVE 23.1%, 95% CI 17.6–28.3%), 201314 (RVE 15.3%, 95% CI 7.8–22.3%), 201415 (RVE 8.9%, 95% CI 5.6–12.1%), and 201617 (RVE 12.6%, 95% CI 6.3–18.4%) seasons, and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines for people ages ≥85 years across all seasons. Similar trends were observed for influenza inpatient stays.


The high-dose versus standard-dose influenza vaccine RVE increases with age.

influenza vaccine, relative vaccine effectiveness, high-dose vaccine, effect of age, Medicare

Topic:  influenza – influenza vaccines – inpatients – medicare – vaccines

Issue Section: Major Article

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; Vaccines; USA.