Strategies for Prevention and Control of Influenza

Topic Information

Dear Colleagues,

Influenza viruses cause annual epidemics and occasional pandemics that result in considerable morbidity and mortality worldwide. Moreover, recent sporadic human infections with avian influenza viruses, such as H5Nx, H7N9, and H9N2 subtypes, have raised the pandemic threat of these viruses. Annual vaccination is one of the most effective ways to prevent seasonal influenza. Current seasonal vaccines comprise three or four different influenza virus strains (H1N1, H3N2, and one or two influenza B viruses), which are reviewed annually and updated to match the antigenicity of the circulating strains. However, the overall efficacy of these vaccines is suboptimal. To improve the current vaccines or develop next-generation vaccines to control influenza, various approaches have been attempted in recent years, including efforts to develop universal vaccines, adjuvanted vaccines, different types of vaccine platforms, cell-based vaccine production, and pre-pandemic vaccines in addition to research on the immunology of influenza viruses. Moreover, basic research promotes a greater understanding of the biology of influenza viruses, which could lead to the establishment of more effective strategies for prevention and control. For this Topic, we seek articles (both reviews and original research) that address this broad area of influenza research.

Dr. Tokiko Watanabe
Dr. Shinji Watanabe
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
International Journal of Molecular Sciences ijms	5.6	7.8	2000	16.3 Days	CHF 2900
Pathogens pathogens	3.7	5.1	2012	16.4 Days	CHF 2700
Tropical Medicine and Infectious Disease tropicalmed	2.9	4.1	2016	19.4 Days	CHF 2700
Vaccines vaccines	7.8	7.0	2013	19.2 Days	CHF 2700
Viruses viruses	4.7	7.1	2009	13.8 Days	CHF 2600

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Published Papers (20 papers)

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17 pages, 4767 KiB  

Open AccessArticle

Identification of Unique and Conserved Neutralizing Epitopes of Vestigial Esterase Domain in HA Protein of the H9N2 Subtype of Avian Influenza Virus

by Xiangyu Huang, Guihu Yin, Yiqin Cai, Jianing Hu, Jingwen Huang, Qingtao Liu and Xiuli Feng

Viruses 2022, 14(12), 2739; https://0-doi-org.brum.beds.ac.uk/10.3390/v14122739 - 08 Dec 2022

Cited by 2 | Viewed by 1465

Abstract

The H9N2 subtype of avian influenza virus (AIV) has been reported to infect not only birds, but also humans. The hemagglutinin (HA) protein is the main surface antigen of AIV and plays an important role in the viral infection. For treatment strategies and [...] Read more.

The H9N2 subtype of avian influenza virus (AIV) has been reported to infect not only birds, but also humans. The hemagglutinin (HA) protein is the main surface antigen of AIV and plays an important role in the viral infection. For treatment strategies and vaccine development, HA protein has been an important target for the development of broadly neutralizing antibodies against influenza A virus. To investigate the vital target determinant cluster in HA protein in this work, HA gene was cloned and expressed in the prokaryotic expression vector pET28a. The spleen lymphocytes from BALC/c mice immunized with the purified recombinant HA protein were fused with SP2/0 cells. After Hypoxanthine-Aminopterin-Thymidine (HAT) medium screening and indirect ELISA detection, six hybridoma cell lines producing anti-HA monoclonal antibodies were screened. The gradually truncated HA gene expression and western blotting were used to identify their major locations in epitopes specific to these monoclonal antibodies. It was found that the epitopes were located in three areas: ¹¹²NVENLEEL¹¹⁹, ¹¹⁷EELRSLFS¹²⁴, and ¹⁷⁰PIQDAQ¹⁷⁵. Epitope ¹¹²NVENLEEL¹¹⁹ has a partial amino acid crossover with ¹¹⁷EELRSLFS¹²⁴, which is located in the vestigial esterase domain “110-helix” of HA, and the monoclonal antibody recognizing these epitopes showed the neutralizing activity, suggesting that the region ¹¹²NVENLEELRSLFS¹²⁴ might be a novel neutralizing epitope. The results of the homology analysis showed that these three epitopes were generally conserved in H9N2 subtype AIV, and will provide valuable insights into H9N2 vaccine design and improvement, as well as antibody-based therapies for treatment of H9N2 AIV infection. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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9 pages, 914 KiB  

Open AccessCommunication

What’s Next for Flu? Out-of-Season Circulation of Influenza Viruses in Southern Italy, August 2022

by Daniela Loconsole, Francesca Centrone, Valerio Aprile, Anna Sallustio, Daniele Casulli, Marisa Accogli, Davide Sacco, Riccardo Zagaria and Maria Chironna

Viruses 2022, 14(12), 2689; https://0-doi-org.brum.beds.ac.uk/10.3390/v14122689 - 30 Nov 2022

Cited by 4 | Viewed by 2118

Abstract

The COVID-19 pandemic has modified the seasonal pattern of respiratory infections. The objective of the present study is to characterize the out-of-season circulation of influenza viruses and an influenza outbreak that occurred in southern Italy in August 2022. Nasopharyngeal swabs collected from patients [...] Read more.

The COVID-19 pandemic has modified the seasonal pattern of respiratory infections. The objective of the present study is to characterize the out-of-season circulation of influenza viruses and an influenza outbreak that occurred in southern Italy in August 2022. Nasopharyngeal swabs collected from patients with influenza-like illnesses (ILI) were tested for the presence of influenza and other respiratory viruses. Epidemiological investigations on 85 patients involved in an influenza outbreak were performed. Sequencing and phylogenetic analysis of hemagglutinin genes was undertaken on samples positive for influenza A. In August 2022, in the Apulia region (Italy), influenza A infection was diagnosed in 19 patients, 18 infected with A/H3N2 and one with A/H1N1pdm09 virus. Seven influenza-positive patients were hospitalized with ILI. A further 17 symptomatic subjects, associated with an influenza outbreak, were also tested; 11 were positive for influenza A/H3N2 virus. Phylogenetic analysis of 12 of the A/H3N2 sequences showed that they all belonged to subclade 3C.2a1b.2a.2. The A/H1N1pdm09 strain belonged to subclade 6B.1A.5a.2. The out-of-season circulation of the influenza virus during the summer months could be linked to changing dynamics in the post-COVID-19 era, as well as to the impact of climate change. Year-round surveillance of respiratory viruses is needed to monitor this phenomenon and to provide effective prevention strategies. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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13 pages, 3291 KiB  

Open AccessArticle

Influenza Vaccine Uptake in the United States before and during the COVID-19 Pandemic

by Ian McGovern, Alina Bogdanov, Katherine Cappell, Sam Whipple and Mendel Haag

Vaccines 2022, 10(10), 1610; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10101610 - 26 Sep 2022

Cited by 12 | Viewed by 1675

Abstract

The COVID-19 pandemic, along with disruptions to routine medical care, brought renewed urgency to public health messaging about the importance of influenza vaccination. This retrospective cohort study used a database of linked claims and electronic medical record data to evaluate clinical and demographic [...] Read more.

The COVID-19 pandemic, along with disruptions to routine medical care, brought renewed urgency to public health messaging about the importance of influenza vaccination. This retrospective cohort study used a database of linked claims and electronic medical record data to evaluate clinical and demographic characteristics and influenza vaccination history associated with changes in influenza vaccine uptake following the start of the COVID-19 pandemic. Influenza vaccine uptake was examined in six seasons (2015–2016 through 2020–2021). Individuals were grouped by vaccination history in the five seasons before 2020–2021. Characteristics of 2020–2021 vaccinated vs. unvaccinated individuals were compared, stratified by vaccination history. Overall influenza vaccination uptake was highest in 2020–2021 (35.4%), following a trend of increasing uptake since 2016–2017 (31.4%). Uptake in 2020–2021 was observed in all age groups except ≥65 years, and the increase was particularly notable in individuals <18 years. In the previous five seasons, individuals ≤17 and >65 years, White, and Asian individuals were most likely, while 18-to-49-year-olds and those with fewer comorbidities were least likely, to be consistently vaccinated. Influenza vaccination status in 2020–2021 aligned with vaccination history; few differences in patient characteristics (age, comorbidities, state of residence) were observed when stratified by vaccination history. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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14 pages, 1880 KiB  

Open AccessArticle

Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice

by Cui-Cui Liu, De-Jian Liu, Xin-Yu Yue, Xiu-Qin Zhong, Xuan Wu, Hai-Yan Chang, Bao-Zhong Wang, Mu-Yang Wan and Lei Deng

Viruses 2022, 14(10), 2109; https://0-doi-org.brum.beds.ac.uk/10.3390/v14102109 - 23 Sep 2022

Cited by 2 | Viewed by 1776

Abstract

Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles [...] Read more.

Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles (cVLPs) co-displaying the truncated C-terminal of DnaK from Escherichia coli and H1 stem or full-length H1 antigen using the baculovirus expression system. Transmission electronic micrography revealed the expression and presentation of H1 stem antigens on the surface of VLPs. Vaccinations of mice with the H1 stem cVLPs induced H1-specific immune responses and provided heterologous immune protection in vivo, which was more effective than vaccinations with VLPs displaying H1 stem alone in protecting mice against weight loss as well as increasing survival rates after lethal influenza viral challenge. The results indicate that the incorporation of the truncated C-terminal of DnaK as an adjuvant protein into the cVLPs significantly enhances the H1-specific immunity and immune protection. We have explicitly identified the VLP platform as an effective way of expressing HA stem antigen and revealed that chimeric VLP is an vaccine vector for developing HA stem-based universal influenza vaccines. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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8 pages, 1671 KiB  

Open AccessArticle

Influenza Viruses Suitable for Studies in Syrian Hamsters

by Shufang Fan, Chunyang Gu, Huihui Kong, Lizheng Guan, Gabriele Neumann and Yoshihiro Kawaoka

Viruses 2022, 14(8), 1629; https://0-doi-org.brum.beds.ac.uk/10.3390/v14081629 - 26 Jul 2022

Cited by 4 | Viewed by 1668

Abstract

Several small animal models, including mice, Syrian hamsters, guinea pigs, and ferrets are used to study the pathogenicity, transmissibility, and antigenicity of seasonal and pandemic influenza viruses. Moreover, animal models are essential for vaccination and challenge studies to evaluate the immunogenicity and protective [...] Read more.

Several small animal models, including mice, Syrian hamsters, guinea pigs, and ferrets are used to study the pathogenicity, transmissibility, and antigenicity of seasonal and pandemic influenza viruses. Moreover, animal models are essential for vaccination and challenge studies to evaluate the immunogenicity and protective efficacy of new vaccines. However, authentic human influenza viruses do not always replicate efficiently in these animal models. Previously, we developed a high-yield A/Puerto Rico/8/34 (PR8-HY) vaccine virus backbone that conferred an increased virus yield to several seasonal influenza vaccines in eukaryotic cells and embryonated chicken eggs. Here, we show that this PR8-HY genetic backbone also increases the replication of several seasonal influenza viruses in Syrian hamsters compared to the authentic viruses. Therefore, the PR8-HY backbone is useful for animal studies to assess the biological properties of influenza viral HA and NA. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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11 pages, 4106 KiB  

Open AccessArticle

An Exemplary National COVID-19 Vaccination: Lessons from Bhutan

by Sangay Phuntsho, Tshokey Tshokey, Mongal Singh Gurung, Sonam Wangdi, Sonam Wangdi and Sonam Wangchuk

Trop. Med. Infect. Dis. 2022, 7(7), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7070131 - 11 Jul 2022

Cited by 1 | Viewed by 2448

Abstract

Vaccination remains a key public health intervention against the COVID-19 pandemic. However, vaccine distribution and coverage are variable between countries due to access and implementation issues. Vaccine inequity was evident with some countries having no access to the vaccines while others have initiated [...] Read more.

Vaccination remains a key public health intervention against the COVID-19 pandemic. However, vaccine distribution and coverage are variable between countries due to access and implementation issues. Vaccine inequity was evident with some countries having no access to the vaccines while others have initiated multiple booster doses. We share Bhutan’s approach to COVID-19 vaccination and lessons learned during the successful conduct of a nationwide vaccination program. As of 12 December 2021, 80.3% of the Bhutanese population have received at least one dose of COVID-19 vaccine and 77.0% have received at least two doses. Considering age groups, 97.2% of adults (18 years) have received at least one dose and 93.6% have received at least two doses. The first dose coverage for the adolescents 12–17 years was 99.7% and second dose coverage was 92.3% since some were not yet due for their second dose at the time of writing this report. The well-established existing national immunization program was especially useful in the implementation of the national COVID-19 vaccination program. The Bhutan Vaccine System, a digital platform for registration and monitoring of vaccination, was rapidly developed and extensively utilized during the campaign. The selfless leadership of the king, the government, and prior detailed planning with multi-sectoral collaboration and coordination, was the key in this exemplary vaccination program. Bhutan has successfully vaccinated children between 5–11 years with high coverage and no serious issues. Many adults have also received first and second booster doses, based on their risks and preferences. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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13 pages, 1647 KiB  

Open AccessArticle

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus

by Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek and Eric A. Weaver

Vaccines 2022, 10(6), 926; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10060926 - 10 Jun 2022

Cited by 2 | Viewed by 2143

Abstract

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from [...] Read more.

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the utility of serotype-switching to enhance the protective immune responses seen with homologous prime-boosting strategies. Immunization with an H2 centralized consensus showed a wide breadth of antibody responses after vaccination, protection against challenge with a divergent human H2 strain, and significantly reduced viral load in the lungs after challenge. Further, serotype switching between two species C adenoviruses enhanced protective antibody titers after heterologous boosting. These data support the notion that an adenoviral-vectored H2 centralized consensus vaccine has the ability to provide broadly cross-reactive immune responses to protect against divergent strains of H2 influenza and prepare for a possible pandemic. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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10 pages, 457 KiB  

Open AccessBrief Report

Attitudes of Healthcare Workers toward Influenza Vaccination in the COVID-19 Era

by Tommaso Sani, Ilaria Morelli, Donatella Sarti, Giovanni Tassinari, Maria Capalbo, Emma Espinosa, Beatrice Gasperini and Emilia Prospero

Vaccines 2022, 10(6), 883; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10060883 - 31 May 2022

Cited by 9 | Viewed by 2092

Abstract

Healthcare workers (HCWs) are reluctant to participate in the influenza vaccination program, despite their high risk to contract and diffuse influenza due to professional exposure. The onset of the COVID-19 pandemic could raise HCW flu vaccination adherence. The aim of this study was [...] Read more.

Healthcare workers (HCWs) are reluctant to participate in the influenza vaccination program, despite their high risk to contract and diffuse influenza due to professional exposure. The onset of the COVID-19 pandemic could raise HCW flu vaccination adherence. The aim of this study was to assess HCW attitudes toward influenza vaccination in the COVID-19 era. A multicenter observational study was carried out in three Italian hospitals (two in Pesaro and one in Fano, Marche region, Italy). Data about HCW influenza vaccination between 2013 and 2021 were extracted from the vaccination registers. An online questionnaire was sent to HCWs from July to October 2020 to assess their opinion about influenza vaccination in terms of knowledge, attitude, and practice during the COVID-19 pandemic. The number of flu-vaccinated HCWs increased from 3.7% in the 2013–2014 flu season to 53.6% in the 2020–2021 flu season (p < 0.001). About 15% (n = 324) of HCWs responded to the online questionnaire, and 30.5% of them declared that they had changed their minds on flu vaccination after the COVID-19 pandemic, deciding to get vaccinated. The COVID-19 pandemic significantly increased HCWs’ attitudes toward flu vaccination. However, flu vaccination adherence remained low and should be improved. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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9 pages, 972 KiB  

Open AccessArticle

A Glycolipid α-GalCer Derivative, 7DW8-5 as a Novel Mucosal Adjuvant for the Split Inactivated Influenza Vaccine

by Huapeng Feng, Ruolin Sun, Guanru Song, Shunfan Zhu, Zhenyu Nie, Liming Lin, Ruonan Yi, Shixiang Wu, Genzhu Wang, Yulong He, Siquan Wang, Pei Wang, Li Wu and Jianhong Shu

Viruses 2022, 14(6), 1174; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061174 - 28 May 2022

Cited by 3 | Viewed by 2095

Abstract

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, [...] Read more.

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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9 pages, 1507 KiB  

Open AccessBrief Report

Out-of-Season Influenza during a COVID-19 Void in the State of Rio de Janeiro, Brazil: Temperature Matters

by Rohini Nott, Trevon L. Fuller, Patrícia Brasil and Karin Nielsen-Saines

Vaccines 2022, 10(5), 821; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050821 - 23 May 2022

Cited by 8 | Viewed by 2862

Abstract

An out-of-season H3N2 type A influenza epidemic occurred in the State of Rio de Janeiro, Brazil during October–November 2021, in between the Delta and Omicron SARS-CoV-2 surges, which occurred in July–October 2021 and January–April 2022, respectively. We assessed the contribution of climate change [...] Read more.

An out-of-season H3N2 type A influenza epidemic occurred in the State of Rio de Janeiro, Brazil during October–November 2021, in between the Delta and Omicron SARS-CoV-2 surges, which occurred in July–October 2021 and January–April 2022, respectively. We assessed the contribution of climate change and influenza immunization coverage in this unique, little publicized phenomenon. State weather patterns during the influenza epidemic were significantly different from the five preceding years, matching typical winter temperatures, associated with the out-of-season influenza. We also found a mismatch between influenza vaccine strains used in the winter of 2021 (trivalent vaccine with two type A strains (Victoria/2570/2019 H1N1, Hong Kong/2671/2019 H3N2) and one type B strain (Washington/02/2019, wild type) and the circulating influenza strain responsible for the epidemic (H3N2 Darwin type A influenza strain). In addition, in 2021, there was poor influenza vaccine coverage with only 56% of the population over 6 months old immunized. Amid the COVID-19 pandemic, we should be prepared for out-of-season outbreaks of other respiratory viruses in periods of COVID-19 remission, which underscore novel disease dynamics in the pandemic era. The availability of year-round influenza vaccines could help avoid unnecessary morbidity and mortality given that antibodies rapidly wane. Moreover, this would enable unimmunized individuals to have additional opportunities to vaccinate during out-of-season outbreaks. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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12 pages, 1600 KiB  

Open AccessArticle

Integrating Electronic Medical Records and Claims Data for Influenza Vaccine Research

by Constantina Boikos, Mahrukh Imran, Simon De Lusignan, Justin R. Ortiz, Peter A. Patriarca and James A. Mansi

Vaccines 2022, 10(5), 727; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050727 - 06 May 2022

Cited by 6 | Viewed by 2423

Abstract

Real-world evidence (RWE) increasingly informs public health and healthcare decisions worldwide. A large database has been created (“Integrated Dataset”) that integrates primary care electronic medical records with pharmacy and medical claims data on >123 million US patients since 2014. This article describes the [...] Read more.

Real-world evidence (RWE) increasingly informs public health and healthcare decisions worldwide. A large database has been created (“Integrated Dataset”) that integrates primary care electronic medical records with pharmacy and medical claims data on >123 million US patients since 2014. This article describes the components of the Integrated Dataset and evaluates its representativeness to the US population and its potential use in evaluating influenza vaccine effectiveness. Representativeness to the US population (2014–2019) was evaluated by comparison with demographic information from the 2019 US census and the National Ambulatory Medical Care Survey (NAMCS). Variables included in the Integrated Dataset were evaluated against World Health Organization (WHO) defined key and non-critical variables for evaluating influenza vaccine performance. The Integrated Dataset contains a variety of information, including demographic data, patient medical history, diagnoses, immunizations, and prescriptions. Distributions of most age categories and sex were comparable with the US Census and NAMCS populations. The Integrated Dataset was less diverse by race and ethnicity. Additionally, WHO key and non-critical variables for the estimation of influenza vaccine effectiveness are available in the Integrated Dataset. In summary, the Integrated Dataset is generally representative of the US population and contains key variables for the assessment of influenza vaccine effectiveness. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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13 pages, 908 KiB  

Open AccessArticle

Medics as a Positive Deviant in Influenza Vaccination: The Role of Vaccine Beliefs, Self-Efficacy and Contextual Variables

by Dorota Włodarczyk and Urszula Ziętalewicz

Vaccines 2022, 10(5), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050723 - 05 May 2022

Cited by 3 | Viewed by 1581

Abstract

The influenza vaccination rate remains unsatisfactorily low, especially in the healthy adult population. The positive deviant approach was used to identify key psychosocial factors explaining the intention of influenza vaccination in medics and compare them with those in non-medics. Methods: There were 709 [...] Read more.

The influenza vaccination rate remains unsatisfactorily low, especially in the healthy adult population. The positive deviant approach was used to identify key psychosocial factors explaining the intention of influenza vaccination in medics and compare them with those in non-medics. Methods: There were 709 participants, as follows: 301 medics and 408 non-medics. We conducted a cross-sectional study in which a multi-module self-administered questionnaire examining vaccination beliefs, risk perception, outcome expectations (gains or losses), facilitators’ relevance, vaccination self-efficacy and vaccination intention was adopted. We also gathered information on access to vaccination, the strength of the vaccination habit and sociodemographic variables. Results: We used SEM and were able to explain 78% of the variance in intention in medics and 56% in non-medics. We identified both direct and indirect effects between the studied variables. In both groups, the intention was related to vaccination self-efficacy, stronger habits and previous season vaccination, but access to vaccines was significant only in non-medics. Conclusions: Applying the positive deviance approach and considering medics as positive deviants in vaccination performance extended the perspective on what factors to focus on in the non-medical population. Vaccination promotion shortly before the flu season should target non- or low-intenders and also intenders by the delivery of balanced information affecting key vaccination cognitions. General pro-vaccine beliefs, which may act as implicit attitudes, should be created in advance to build proper grounds for specific outcome expectations and facilitators’ recognition. It should not be limited only to risk perception. Some level of evidence-based critical beliefs about vaccination can be beneficial. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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12 pages, 1261 KiB  

Open AccessArticle

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents

by Michelle Clarke, Suja M. Mathew, Lynne C. Giles, Alexia S. Pena, Ian G. Barr, Peter C. Richmond and Helen S. Marshall

Vaccines 2022, 10(5), 699; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050699 - 29 Apr 2022

Cited by 4 | Viewed by 1889

Abstract

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ [...] Read more.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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8 pages, 1049 KiB  

Open AccessArticle

Influenza Vaccine Utilization: A Comparison between Urban and Rural Counties in Florida

by Abdullah A. Alalwan

Vaccines 2022, 10(5), 669; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10050669 - 23 Apr 2022

Cited by 3 | Viewed by 1833

Abstract

(1) Background: The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend that every person aged six months and over receive the influenza vaccine every year. Previous studies indicate that rural-area residents have less access to preventative health [...] Read more.

(1) Background: The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend that every person aged six months and over receive the influenza vaccine every year. Previous studies indicate that rural-area residents have less access to preventative health care services. This study aims to examine the variation in influenza vaccine use among rural and urban counties in Florida. (2) Methods: The study studied 24,116 participants from the Behavioral Risk Factor Surveillance System database. The study included only patients who live in Florida. We performed logistic regression analysis using survey procedures available in SAS^®. Our regression model assessed the association between receiving the influenza vaccine and county status, age, income level, education level, and health coverage. We used ArcGIS software to create prevalence and vaccination maps. (3) Results: Of the total number of the study participants, 45.31% were residents of rural counties, and 54.69% were residents of urban counties. The logistic regression model showed no significant association between residing in rural counties and not receiving influenza vaccine in the past year (−0.05560, p-value = 0.0549). However, we found significant associations between not receiving influenza vaccine and age, high education level, and not having health care coverage (−0.0412, p-value < 0.0001; −0.04462, p-value = 0.0139; and 0.4956, p-value < 0.0001, respectively). (4)Conclusions: Our study did not find an association between influenza vaccine use among rural and urban residence. Increasing age, higher education, and having health care insurance had positive associations with influenza vaccine use. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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11 pages, 1282 KiB  

Open AccessArticle

Influenza Vaccination Effectiveness in Paediatric ‘Healthy’ Patients: A Population-Based Study in Italy

by Anna Cantarutti, Elisa Barbieri, Fabio Didonè, Antonio Scamarcia, Carlo Giaquinto and Giovanni Corrao

Vaccines 2022, 10(4), 582; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10040582 - 10 Apr 2022

Cited by 1 | Viewed by 2107

Abstract

Background: Seasonal influenza can cause serious morbidity, mortality, and financial burden in pediatric and adult populations. The influenza vaccine (IV) is considered the most effective way to prevent influenza and influenza-like-illness (ILI) complications. Objective: To assess the effectiveness of the IV in a [...] Read more.

Background: Seasonal influenza can cause serious morbidity, mortality, and financial burden in pediatric and adult populations. The influenza vaccine (IV) is considered the most effective way to prevent influenza and influenza-like-illness (ILI) complications. Objective: To assess the effectiveness of the IV in a cohort of healthy children in Italy. Methods: From the Pedianet database, all healthy children aged six months–14 years between 2009–2019 were enrolled. Cox proportional-hazards models were fitted to estimate hazard ratios and the 95% confidence interval for the association between IV exposure during each season of interest (from October to April of each year) with incident influenza/ILI. Exposure was considered as a time-varying variable. Vaccine effectiveness (VE) was calculated as (1-HR) × 100. The additive and prolonged effects of IV were evaluated across the seasons. Results: We found a high IV effectiveness among healthy children. No additional or prolonged effects were found. Conclusion: Our data indicates that IV was effective in preventing influenza/ILI in healthy children. Therefore, IV should be encouraged and provided free of charge to healthy children in all the Italian regions every year, reducing disease spread and lowering the burden on the pediatric population. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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18 pages, 5813 KiB  

Open AccessArticle

Antiviral Effects of ABMA and DABMA against Influenza Virus In Vitro and In Vivo via Regulating the Endolysosomal Pathway and Autophagy

by Hongtao Liu, Chunlai Jiang, Yu Wu, Min Wu, Jiaxin Wu, Guanshu Zhao, Jie Sun, Xinyu Huang, Jiemin Li, Rui Sheng, Julien Barbier, Jean-Christophe Cintrat, Daniel Gillet and Weiheng Su

Int. J. Mol. Sci. 2022, 23(7), 3940; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073940 - 01 Apr 2022

Cited by 4 | Viewed by 2738

Abstract

Influenza virus is an acute and highly contagious respiratory pathogen that causes great concern to public health and for which there is a need for extensive drug discovery. The small chemical compound ABMA and its analog DABMA, containing an adamantane or a dimethyl-adamantane [...] Read more.

Influenza virus is an acute and highly contagious respiratory pathogen that causes great concern to public health and for which there is a need for extensive drug discovery. The small chemical compound ABMA and its analog DABMA, containing an adamantane or a dimethyl-adamantane group, respectively, have been demonstrated to inhibit multiple toxins (diphtheria toxin, Clostridium difficile toxin B, Clostridium sordellii lethal toxin) and viruses (Ebola, rabies virus, HSV-2) by acting on the host’s vesicle trafficking. Here, we showed that ABMA and DABMA have antiviral effects against both amantadine-sensitive influenza virus subtypes (H1N1 and H3N2), amantadine-resistant subtypes (H3N2), and influenza B virus with EC₅₀ values ranging from 2.83 to 7.36 µM (ABMA) and 1.82 to 6.73 µM (DABMA), respectively. ABMA and DABMA inhibited the replication of influenza virus genomic RNA and protein synthesis by interfering with the entry stage of the virus. Molecular docking evaluation together with activity against amantadine-resistant influenza virus strains suggested that ABMA and DABMA were not acting as M2 ion channel blockers. Subsequently, we found that early internalized H1N1 virions were retained in accumulated late endosome compartments after ABMA treatment. Additionally, ABMA disrupted the early stages of the H1N1 life cycle or viral RNA synthesis by interfering with autophagy. ABMA and DABMA protected mice from an intranasal H1N1 challenge with an improved survival rate of 67%. The present study suggests that ABMA and DABMA are potential antiviral leads for the development of a host-directed treatment against influenza virus infection. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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9 pages, 1089 KiB  

Open AccessArticle

Characterization of H9N2 Avian Influenza Viruses Isolated from Poultry Products in a Mouse Model

by Jurika Murakami, Akihiro Shibata, Gabriele Neumann, Masaki Imai, Tokiko Watanabe and Yoshihiro Kawaoka

Viruses 2022, 14(4), 728; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040728 - 30 Mar 2022

Cited by 2 | Viewed by 2204

Abstract

Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are not yet enzootic; however, [...] Read more.

Low pathogenic H9N2 avian influenza viruses have spread in wild birds and poultry worldwide. Recently, the number of human cases of H9N2 virus infection has increased in China and other countries, heightening pandemic concerns. In Japan, H9N2 viruses are not yet enzootic; however, avian influenza viruses, including H5N1, H7N9, H5N6, and H9N2, have been repeatedly detected in raw poultry meat carried by international flight passengers from Asian countries to Japan. Although H9N2 virus-contaminated poultry products intercepted by the animal quarantine service at the Japan border have been characterized in chickens and ducks, the biological properties of those H9N2 viruses in mammals remain unclear. Here, we characterized the biological features of two H9N2 virus isolates [A/chicken/Japan/AQ-HE28-50/2016 (Ck/HE28-50) and A/chicken/Japan/AQ-HE28-57/2016 (Ck/HE28-57)] in a mouse model. We found that these H9N2 viruses replicate well in the respiratory tract of infected mice without adaptation, and that Ck/HE28-57 caused body weight loss in the infected mice. Our results indicate that H9N2 avian influenza viruses isolated from raw chicken meat products illegally brought to Japan can potentially infect and cause disease in mammals. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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16 pages, 2125 KiB  

Open AccessArticle

KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells

by Huapeng Feng, Ruonan Yi, Shixiang Wu, Genzhu Wang, Ruolin Sun, Liming Lin, Shunfan Zhu, Zhenyu Nie, Yulong He, Siquan Wang, Pei Wang, Jianhong Shu and Li Wu

Viruses 2022, 14(4), 689; https://0-doi-org.brum.beds.ac.uk/10.3390/v14040689 - 26 Mar 2022

Cited by 1 | Viewed by 2305

Abstract

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role [...] Read more.

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-β production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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17 pages, 1964 KiB  

Open AccessArticle

Cost-Effectiveness of Influenza Vaccination Strategies in Adults: Older Adults Aged ≥65 Years, Adults Aged 50–64 Years, and At-Risk Adults Aged 19–64 Years

by Min Joo Choi, Gyeongseon Shin, Daewon Kang, Jae-Ok Lim, Yun-Kyung Kim, Won Suk Choi, Jae-Won Yun, Ji Yun Noh, Joon Young Song, Woo Joo Kim, Sang-Eun Choi and Hee Jin Cheong

Vaccines 2022, 10(3), 445; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10030445 - 14 Mar 2022

Cited by 5 | Viewed by 4296

Abstract

The high disease burden of influenza in elderly and chronically ill adults may be due to the suboptimal effectiveness and mismatch of the conventional trivalent influenza vaccine (TIV). This study evaluated the cost-effectiveness of quadrivalent (QIV), adjuvanted trivalent (ATIV), and high-dose quadrivalent (HD-QIV) [...] Read more.

The high disease burden of influenza in elderly and chronically ill adults may be due to the suboptimal effectiveness and mismatch of the conventional trivalent influenza vaccine (TIV). This study evaluated the cost-effectiveness of quadrivalent (QIV), adjuvanted trivalent (ATIV), and high-dose quadrivalent (HD-QIV) vaccines versus TIV used under the current Korean National Immunization Program (NIP) in older adults aged ≥65 years. We also evaluated the cost-effectiveness of programs for at-risk adults aged 19–64 and adults aged 50–64. A one-year static population model was used to compare the costs and outcomes of alternative vaccination programs in each targeted group. Influenza-related parameters were derived from the National Health Insurance System claims database; other inputs were extracted from the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed from a societal perspective. In the base case analysis (older adults aged ≥65 years), HD-QIV was superior, with the lowest cost and highest utility. Compared with TIV, ATIV was cost-effective (ICER $34,314/quality-adjusted life-year [QALY]), and QIV was not cost-effective (ICER $46,486/QALY). The cost-effectiveness of HD-QIV was robust for all parameters except for vaccine cost. The introduction of the influenza NIP was cost-effective or even cost-saving for the remaining targeted gr3oups, regardless of TIV or QIV. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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19 pages, 4275 KiB  

Open AccessArticle

Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection

by Ajitanuj Rattan, Chantelle L. White, Sean Nelson, Max Eismann, Herbey Padilla-Quirarte, Maryah A. Glover, Thamotharampillai Dileepan, Bindumadhav M. Marathe, Elena A. Govorkova, Richard J. Webby, Katherine A. Richards and Andrea J. Sant

Pathogens 2022, 11(2), 251; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020251 - 15 Feb 2022

Cited by 4 | Viewed by 2444

Abstract

The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza [...] Read more.

The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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