Inactivated pandemic 2009 H1N1 influenza A virus human vaccines have different efficacy after homologous challenge in the ferret model

Vidaña, Beatriz; Brookes, Sharon M; Everett, Helen; Garçon, Fanny; Núñez, Alejandro; Engelhardt, Othmar G.; Major, Diane; Höschler, Katja; Brown, Ian H.; Zambon, Maria

doi:10.1111/irv.12784

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…The ferret has played an important role in infectious viral disease modelling for e.g. influenza A viruses and SARS-CoV-2 [27,35,45]. Hepatic lesions are occasionally reported from laboratory ferrets, including hepatic lipidosis, portal hepatitis, localized hepatic necrosis or abscessation, and these changes are considered non-specific for animal modelling [35,46,47].…”

Section: Discussionmentioning

confidence: 99%

Subclinical hepatitis E virus infection in laboratory ferrets in the UK

Lean

Leblond

Byrne

et al. 2022

Journal of General Virology

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Ferrets are widely used for experimental modelling of viral infections. However, background disease in ferrets could potentially confound intended experimental interpretation. Here we report the detection of a subclinical infection of ferret hepatitis E virus (FRHEV) within a colony sub-group of female laboratory ferrets that had been enrolled on an experimental viral infection study (non-hepatitis). Lymphoplasmacytic cuffing of periportal spaces was identified on histopathology but was negative for the RNA and antigens of the administered virus. Follow-up viral metagenomic analysis conducted on liver specimens revealed sequences attributed to FRHEV and these were confirmed by reverse-transcriptase polymerase chain reaction. Further genomic analysis revealed contiguous sequences spanning 79–95 % of the FRHEV genome and that the sequences were closely related to those reported previously in Europe. Using in situ hybridization by RNAScope, we confirmed the presence of HEV-specific RNA in hepatocytes. The HEV open reading frame 2 (ORF2) protein was also detected by immunohistochemistry in the hepatocytes and the biliary canaliculi. In conclusion, the results of our study provide evidence of background infection with FRHEV in laboratory ferrets. As this infection can be subclinical, we recommend routine monitoring of ferret populations using virological and liver function tests to avoid incorrect causal attribution of any liver disease detected in in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Subclinical hepatitis E virus infection in laboratory ferrets in the UK

Lean

Leblond

Byrne

et al. 2022

Journal of General Virology

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“…Interestingly, a similar study conducted in ferrets challenged six weeks after the initial vaccination, generated results consistent with our own findings with NG34 + CAF ® 01 vaccine. This study showed that pdm09 H1N1 vaccines reduced (adjuvanted split vaccine) or had no effect (non-adjuvanted whole vaccine) on the viral shedding from the upper respiratory tract, although the adjuvanted split vaccine did prevent viral replication in the lower respiratory tract of ferrets [ 46 , 47 ]. This suggest that local immunity may play a role for viral shedding but less for pulmonary disease.…”

Section: Discussionmentioning

confidence: 99%

Immune Responses to Pandemic H1N1 Influenza Virus Infection in Pigs Vaccinated with a Conserved Hemagglutinin HA1 Peptide Adjuvanted with CAF®01 or CDA/αGalCerMPEG

et al. 2021

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This study aimed to evaluate the immune response and protection correlates against influenza virus (IV) infection in pigs vaccinated with the novel NG34 HA1 vaccine candidate adjuvanted with either CAF®01 or CDA/αGalCerMPEG (αGCM). Two groups of six pigs each were vaccinated intramuscularly twice with either NG34 + CAF®01 or NG34 + CDA/αGCM. As controls, groups of animals (n = 6 or 4) either non-vaccinated or vaccinated with human seasonal trivalent influenza vaccine or NG34 + Freund’s adjuvant were included in the study. All animal groups were challenged with the 2009 pandemic (pdm09) strain of H1N1 (total amount of 7 × 106 TCID50/mL) via intranasal and endotracheal routes 21 days after second vaccination. Reduced consolidated lung lesions were observed both on days three and seven post-challenge in the animals vaccinated with NG34 + CAF®01, whereas higher variability with relatively more severe lesions in pigs of the NG34 + CDA/αGCM group on day three post-infection. Among groups, animals vaccinated with NG34 + CDA/αGCM showed higher viral loads in the lung at seven days post infection whereas animals from NG34 + CAF®01 completely abolished virus from the lower respiratory tract. Similarly, higher IFNγ secretion and stronger IgG responses against the NG34 peptide in sera was observed in animals from the NG34 + CAF®01 group as compared to the NG34 + CDA/αGCM. NG34-vaccinated pigs with adjuvanted CAF®01 or CDA/αGCM combinations resulted in different immune responses as well as outcomes in pathology and viral shedding.

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“…Early studies using the ferret model showed that cellular immune responses, especially cytotoxicity T cells, play an important role in recovery from influenza virus infection [96,97]. Furthermore, several influenza vaccine platforms have been studied using ferret models [81][82][83]86,87,[98][99][100]. A study by Holzer et al described differential protective efficacy of the Signal Minus FLU vaccine candidate in ferrets and pigs [101].…”

Section: Pathogenesis and Transmissionmentioning

confidence: 99%

Animal Models for Influenza Research: Strengths and Weaknesses

Nguyen

Rollon

Choi

2021

Viruses

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Influenza remains one of the most significant public health threats due to its ability to cause high morbidity and mortality worldwide. Although understanding of influenza viruses has greatly increased in recent years, shortcomings remain. Additionally, the continuous mutation of influenza viruses through genetic reassortment and selection of variants that escape host immune responses can render current influenza vaccines ineffective at controlling seasonal epidemics and potential pandemics. Thus, there is a knowledge gap in the understanding of influenza viruses and a corresponding need to develop novel universal vaccines and therapeutic treatments. Investigation of viral pathogenesis, transmission mechanisms, and efficacy of influenza vaccine candidates requires animal models that can recapitulate the disease. Furthermore, the choice of animal model for each research question is crucial in order for researchers to acquire a better knowledge of influenza viruses. Herein, we reviewed the advantages and limitations of each animal model—including mice, ferrets, guinea pigs, swine, felines, canines, and non-human primates—for elucidating influenza viral pathogenesis and transmission and for evaluating therapeutic agents and vaccine efficacy.

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Inactivated pandemic 2009 H1N1 influenza A virus human vaccines have different efficacy after homologous challenge in the ferret model

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 4 publications

References 24 publications

Subclinical hepatitis E virus infection in laboratory ferrets in the UK

Subclinical hepatitis E virus infection in laboratory ferrets in the UK

Immune Responses to Pandemic H1N1 Influenza Virus Infection in Pigs Vaccinated with a Conserved Hemagglutinin HA1 Peptide Adjuvanted with CAF®01 or CDA/αGalCerMPEG

Animal Models for Influenza Research: Strengths and Weaknesses

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