#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, https://doi.org/10.1093/infdis/jiz152

Published: 17 July 2019

 

Abstract

Background

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

Methods

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.

Results

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.

Conclusions

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.

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#Azithromycin, a 15-membered #macrolide #antibiotic, inhibits #influenza A #H1N1pdm09 virus #infection by interfering with virus internalization process (J Antibit (Tokyo), abstract)

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

J Antibiot (Tokyo). 2019 Jul 12. doi: 10.1038/s41429-019-0204-x. [Epub ahead of print]

Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process.

Tran DH1,2, Sugamata R1,2,3, Hirose T4, Suzuki S1,2,3, Noguchi Y4, Sugawara A4,5, Ito F2, Yamamoto T2, Kawachi S2,3, Akagawa KS4, Ōmura S4, Sunazuka T4, Ito N6, Mimaki M6, Suzuki K7,8,9.

Author information: 1 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 2 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 3 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 4 Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo, 108-8641, Japan. 5 Graduate School of Pharmaceutical Sciences, Tohoku University, Aza-Aoba 6-3, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. 6 The Pediatric Department, Teikyo Hospital University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. 7 Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 8 Asia International Institute of Infectious Disease Control (ADC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp. 9 General Medical Education and Research Center (G-MEC), Teikyo University, Kaga 2-11-1, Itabashi-ku, Tokyo, 173-8605, Japan. suzuki-k@med.teikyo-u.ac.jp.

 

Abstract

The pandemic influenza 2009 (A(H1N1)pdm09) virus currently causes seasonal and annual epidemic outbreaks. The widespread use of anti-influenza drugs such as neuraminidase and matrix protein 2 (M2) channel inhibitors has resulted in the emergence of drug-resistant influenza viruses. In this study, we aimed to determine the anti-influenza A(H1N1)pdm09 virus activity of azithromycin, a re-positioned macrolide antibiotic with potential as a new anti-influenza candidate, and to elucidate its underlying mechanisms of action. We performed in vitro and in vivo studies to address this. Our in vitro approaches indicated that progeny virus replication was remarkably inhibited by treating viruses with azithromycin before infection; however, azithromycin administration after infection did not affect this process. We next investigated the steps inhibited by azithromycin during virus invasion. Azithromycin did not affect attachment of viruses onto the cell surface, but blocked internalization into host cells during the early phase of infection. We further demonstrated that azithromycin targeted newly budded progeny virus from the host cells and inactivated their endocytic activity. This unique inhibitory mechanism has not been observed for other anti-influenza drugs, indicating the potential activity of azithromycin before and after influenza virus infection. Considering these in vitro observations, we administered azithromycin intranasally to mice infected with A(H1N1)pdm09 virus. Single intranasal azithromycin treatment successfully reduced viral load in the lungs and relieved hypothermia, which was induced by infection. Our findings indicate the possibility that azithromycin could be an effective macrolide for the treatment of human influenza.

PMID:  31300721  DOI: 10.1038/s41429-019-0204-x

Keywords: Antibiotics; Azithromycin; Influenza A; H1N1pdm09.

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#Health #outcomes of young #children born to #mothers who received 2009 #pandemic #H1N1 #influenza #vaccination during #pregnancy: retrospective cohort study (BMJ, abstract)

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

BMJ. 2019 Jul 10;366:l4151. doi: 10.1136/bmj.l4151.

Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study.

Walsh LK1,2, Donelle J3, Dodds L4, Hawken S2,3,5, Wilson K2,3,5, Benchimol EI2,3,6, Chakraborty P2,6, Guttmann A3,7,8, Kwong JC3,7,9,10, MacDonald NE4, Ortiz JR11, Sprague AE1,2,6, Top KA4, Walker MC1,2,5, Wen SW2,5, Fell DB12,3,6.

Author information: 1 Better Outcomes Registry & Network, Ottawa, ON, Canada. 2 University of Ottawa, Ottawa, ON, Canada. 3 ICES, Toronto, ON, Canada. 4 Dalhousie University, Halifax, NS, Canada. 5 Ottawa Hospital Research Institute, Ottawa, ON, Canada. 6 Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada. 7 Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 8 Hospital for Sick Children, Toronto, ON, Canada. 9 Public Health Ontario, Toronto, ON, Canada. 10 Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada. 11 University of Maryland School of Medicine, Baltimore, MD, USA. 12 University of Ottawa, Ottawa, ON, Canada dfell@cheo.on.ca.

 

Abstract

OBJECTIVE:

To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood.

DESIGN:

Retrospective cohort study.

SETTING:

Population based birth registry linked with health administrative databases in the province of Ontario, Canada.

PARTICIPANTS:

All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes.

MAIN OUTCOME MEASURES:

Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding.

RESULTS:

Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups.

CONCLUSIONS:

No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PMID: 31292120 DOI: 10.1136/bmj.l4151

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.

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Serial Section Array Scanning Electron Microscopy Analysis of Cells from #Lung #Autopsy #Specimens Following #Fatal A/ #H1N1pdm09 #Influenza Virus #Infection (J Virol., abstract)

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

Serial Section Array Scanning Electron Microscopy Analysis of Cells from Lung Autopsy Specimens Following Fatal A/H1N1 2009 Pandemic Influenza Virus Infection

Michiyo Kataoka, Kinji Ishida, Katsutoshi Ogasawara, Takayuki Nozaki, Yoh-ichi Satoh, Tetsutaro Sata, Yuko Sato, Hideki Hasegawa, Noriko Nakajima

DOI: 10.1128/JVI.00644-19

 

ABSTRACT

A/H1N1 2009 pandemic influenza virus (A/H1N1/pdm09) was first identified as a novel pandemic influenza A virus (IAV) in 2009. Previously, we reported that many viral antigens were detected in type II alveolar epithelial cells (AEC-IIs) within autopsied lung tissue from a patient with A/H1N1/pdm09 pneumonia. It is important to identify the association between the virus and host cells to elucidate the pathogenesis of IAV pneumonia. To investigate the distribution of virus particles and morphological changes in host cells, the autopsied lung specimens from this patient were examined using transmission electron microscopy (TEM) and a novel scanning electron microscopy (SEM) method. We focused on AEC-IIs as viral antigen-positive cells, and on monocytes/macrophages (Ms/MΦs) and neutrophils (Neus) as innate immune cells. We identified virus particles and intranuclear dense tubules, which are associated with matrix 1 (M1) proteins from IAV. Large-scale two-dimensional observation was enabled by digitally ‘stitching’ together contiguous SEM images. A single whole cell analysis using a serial section array (SSA)-SEM identified virus particles in vesicles within the cytoplasm and/or around the cell surface of AEC-IIs, Ms/MΦs, and Neus; however, intranuclear dense tubules were found only in AEC-IIs. Computer-assisted processing of SSA-SEM images from each cell type enabled 3D modeling of the distribution of virus particles within an ACE-II, a M/MΦ, and a Neu.

 

IMPORTANCE

Generally, it is difficult to observe IAV particles in post-mortem samples from patients with seasonal influenza. In fact, only a few viral antigens are detected in bronchial epithelial cells from autopsied lung sections. Previously, we detected many viral antigens in AEC-IIs from the lung. This was because the majority of A/H1N1/pdm09 in the lung tissue harbored an aspartic acid to glycine substitution at position 222 (D222G) of the hemagglutinin protein. A/H1N1/pdm09 harboring the D222G substitution has a receptor-binding preference for α-2,3-linked sialic acids expressed on human AECs and infects them in the same way as H5N1 and H7N9 avian IAVs. Here, we report the first successful observation of virus particles not only in AEC-IIs, but also in Ms/MΦs and Neus, using electron microscopy. The finding of a M/MΦ harboring numerous virus particles within vesicles and at the cell surface suggests that Ms/MΦs are involved in the pathogenesis of IAV primary pneumonia.

Copyright © 2019 Kataoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Influenza A; Seasonal Influenza; Pandemic Influenza; Avian Influenza; H1N1pdm09; H5N1; H7N9; Viral pathogenesis.

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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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Investigation of an #outbreak of acute #respiratory #disease in an #indigenous village in #Brazil: Contribution of #Influenza A #H1N1pdm09 and human #RSV (PLoS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Investigation of an outbreak of acute respiratory disease in an indigenous village in Brazil: Contribution of Influenza A(H1N1)pdm09 and human respiratory syncytial viruses

Andrey Moreira Cardoso  , Paola Cristina Resende , Enny S. Paixao , Felipe G. Tavares , Yasmin N. Farias , Carla Tatiana G. Barreto , Lídia N. Pantoja , Fernanda L. Ferreira , André Luiz Martins , Ângela Barbosa Lima , Daniella A. Fernandes , Patrícia Machado Sanches , Walquiria A. F. Almeida , Laura C. Rodrigues , Marilda M. Siqueira

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Published: July 8, 2019 / DOI: https://doi.org/10.1371/journal.pone.0218925

 

Abstract

Analyses of the 2009 H1N1 influenza pandemic and post-pandemic years showed high attack rates and severity among indigenous populations. This study presents the characteristics of the first documented influenza outbreak in indigenous peoples in Brazil, that occurred from 30th March to 14th April 2016 in a Guarani village in Southeast Region. Acute respiratory infections were prospectively investigated. The majority of the 73 cases were influenza-like illness (ILI) (63.0%) or severe acute respiratory infection (SARI) (20.5%). The ILI+SARI attack rate (35.9%) decreased with increasing age. There was a high influenza vaccination rate (86.3%), but no statistically significant difference in vaccination rates between severe and non-severe cases was seen (p = 0.334). Molecular analyses of 19.2% of the cases showed 100% positivity for influenza A(H1N1)pdm09 and/or hRSV. Influenza A(H1N1)pdm09 was included in the 6B.1 genetic group, a distinct cluster with 13 amino acid substitutions of A/California/07/2009-like. The hRSV were clustered in the BA-like genetic group. The early arrival of the influenza season overlapping usual hRSV season, the circulation of a drifted influenza virus not covered by vaccine and the high prevalence of risk factors for infection and severity in the village jointly can explain the high attack rate of ARI, even with a high rate of influenza vaccination. The results reinforce the importance of surveillance of respiratory viruses, timely vaccination and controlling risk factors for infection and severity of in the indigenous populations in order to preventing disease and related deaths, particularly in children.

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Citation: Cardoso AM, Resende PC, Paixao ES, Tavares FG, Farias YN, Barreto CTG, et al. (2019) Investigation of an outbreak of acute respiratory disease in an indigenous village in Brazil: Contribution of Influenza A(H1N1)pdm09 and human respiratory syncytial viruses. PLoS ONE 14(7): e0218925. https://doi.org/10.1371/journal.pone.0218925

Editor: Eric HY Lau, The University of Hong Kong, CHINA

Received: September 27, 2018; Accepted: June 13, 2019; Published: July 8, 2019

Copyright: © 2019 Cardoso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Influenza A(H1N1)pdm09 sequences obtained in this study were deposited in the Global Initiative on Sharing All Influenza Data (GISAID) database under the accession numbers EPI_ISL_271538, EPI_ISL_271539, EPI_ISL_274050, EPI_ISL_274051 and EPI_ISL_274061 and the hRSV strains in Genbank under the accession numbers (MH719234 and MH719235). Meritorious proposals for access to data will be considered subject to ethical and legal restrictions, the terms of the original informed consent agreement with participant community, and Guarani community protocols for authorizing studies. Due to the small size of the study community, the minimal dataset cannot be adequately anonymized to permit open access while protecting participants’ identities. Data requests may be sent to Reinaldo Souza dos Santos, Head of Department, Departamento de Endemias Samuel Pessoa, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, located at Rua Leopoldo Bulhões 1480, Rio de Janeiro, RJ 21041-210, Brazil. Phone: +55 (21) 2598-2683. Email: rssantos@ensp.fiocruz.br.

Funding: This project was funded by the following institutions: Received by AMC – National Research Council (CNPq – www.cnpq.br) Universal 14/2011 – 47.4008/2011-8 and CNPq Universal 01/2016 – 428284/2016-7; Oswaldo Cruz Foundation (Fiocruz – www.fiocruz.br) – INOVA ENSP II 2013 – 25388.000556/2013-52, PAPES VII – Young scientist 2014 – 401789/2015-2 and ENSP 2016/2018 – 25388.000526/2017-70; Research Foundation of the State of Rio de Janeiro (FAPERJ – www.faperj.br) PPSUS FAPERJ/SES-RJ/MS-DECIT/CNPq 35/2013-E-26/110.275/2014; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES – www.capes.gov.br) – Finance Code 001; Received by MMS – CNPq Universal 431975/2016-7, used for the molecular analysis. 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; H1N1pdm09; RSV; SARI; Brazil.

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#Haemagglutinin #stability was not the primary cause of the reduced #effectiveness of #LAIV against A/ #H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons (Vaccine, abstract)

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

Vaccine. 2019 Jul 3. pii: S0264-410X(19)30777-7. doi: 10.1016/j.vaccine.2019.06.016. [Epub ahead of print]

Haemagglutinin stability was not the primary cause of the reduced effectiveness of live attenuated influenza vaccine against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.

Parker L1, Ritter L2, Wu W2, Maeso R2, Bright H2, Dibben O2.

Author information: 1 Flu-BPD, AstraZeneca, Liverpool, UK. Electronic address: parkerla@medimmune.com. 2 Flu-BPD, AstraZeneca, Liverpool, UK.

 

Abstract

During the 2013-2014 influenza season, the quadrivalent live attenuated influenza vaccine (QLAIV), had lower than expected vaccine effectiveness (VE) against circulating A/H1N1pdm09 viruses in the USA. The underlying reason proposed for this was that the A/H1N1pdm09 vaccine strain, A/California/07/2009 (A/CA09), had a thermally unstable haemagglutinin (HA) protein. Consequently, a new A/H1N1pdm09 candidate strain, A/Bolivia/559/2013 (A/BOL13), was developed for inclusion in the 2015-2016 QLAIV. A key parameter for selection of A/BOL13 was its more thermostable HA phenotype compared with A/CA09. During the 2015-2016 season, QLAIV containing A/BOL13 was found in some studies to have improved, but still with suboptimal, VE against circulating A/H1N1pdm09 viruses and was not recommended for use by the CDC in the US market in the 2016-2017 influenza season. This suggested that improved HA thermostability had not entirely resolved the reduced VE observed. One hypothesis for this was that, by improving thermostability, the A/BOL13 HA protein had been over-stabilised, compromising its activation at the low endosomal pH required for successful viral entry. Here we demonstrate that, while the A/BOL13 HA protein is more stable than that of A/CA09, its thermal and pH stability were comparable with historically efficacious LAIV strains, suggesting that the HA had not been over-stabilised. Furthermore, studies simulating potential heat exposure during distribution by exposing QLAIV nasal sprayers to 33 °C for 4 h showed that, while remaining within product specification, A/CA09 viral potency was statistically decreased after 12 weeks at 2-8 °C. These data suggest that although unfavourable HA protein stability may have contributed to the reduced VE of A/CA09 in 2013-2014, it was unlikely to have affected A/BOL13 in 2015-2016. We conclude that HA stability was not the primary cause of the reduced effectiveness of LAIV against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.

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

KEYWORDS: 2009 pandemic A/H1N1 (A/H1N1pdm09); Haemagglutinin; Influenza; Live attenuated influenza vaccine; Thermostability; Vaccine effectiveness; pH stability

PMID: 31279567 DOI: 10.1016/j.vaccine.2019.06.016

Keywords: Seasonal Influenza; H1N1pdm09; Vaccines.

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