Immune Imprinting in the Influenza Ferret Model

Skarlupka, Amanda L.; Ross, Ted M.

doi:10.3390/vaccines8020173

Cited by 12 publications

(9 citation statements)

References 121 publications

(184 reference statements)

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“…Apart from the influence of sialic acids on the immune system, humans can already have pre-existing immunity to a broad spectrum of influenza strains. This pre-existing immunity is often lacking in animal models, although pre-immune mice and ferret models are available [ 72 , 73 , 74 , 75 , 76 ].…”

Section: Resultsmentioning

confidence: 99%

N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Spruit

Nemanichvili

Okamatsu

et al. 2021

Viruses

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The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)−/− knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.

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Section: Resultsmentioning

confidence: 99%

N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Spruit

Nemanichvili

Okamatsu

et al. 2021

Viruses

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“…Laboratory infected ferrets shed SARS-CoV-2 via saliva, urine, and nasal washes and potential airborne transmission was possible to naïve ferrets [ 180 , 183 ]. The advantages of using ferrets as a model animal for vaccine development are that they can be used for evaluating cough and fever symptoms and they have an extensive history of respiratory viral research [ 184 , 185 ]. The downsides of ferrets as a model animal are that it remains unclear if edema and serious lung infection can be caused by SARS-CoV-2 in them [ 107 ].…”

Section: Animal Host Diversity Of Sars-cov-2mentioning

confidence: 99%

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

Hedman¹,

Krawczyk

Helmy

et al. 2021

Pathogens

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Emerging infectious diseases present great risks to public health. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become an urgent public health issue of global concern. It is speculated that the virus first emerged through a zoonotic spillover. Basic research studies have suggested that bats are likely the ancestral reservoir host. Nonetheless, the evolutionary history and host susceptibility of SARS-CoV-2 remains unclear as a multitude of animals has been proposed as potential intermediate or dead-end hosts. SARS-CoV-2 has been isolated from domestic animals, both companion and livestock, as well as in captive wildlife that were in close contact with human COVID-19 cases. Currently, domestic mink is the only known animal that is susceptible to a natural infection, develop severe illness, and can also transmit SARS-CoV-2 to other minks and humans. To improve foundational knowledge of SARS-CoV-2, we are conducting a synthesis review of its host diversity and transmission pathways. To mitigate this COVID-19 pandemic, we strongly advocate for a systems-oriented scientific approach that comprehensively evaluates the transmission of SARS-CoV-2 at the human and animal interface.

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“…It has been hypothesized that the infant immune system may facilitate a broader immune response than those of the more immunologically mature ages [ 14 ]. In our discussion of age and ferret models for influenza, it is important that we mention that ferrets have been proposed as a model for understanding influenza virus imprinting of the immune system [ 67 , 71 ]. With increased need to understand influenza imprinting for pathogenesis modeling and universal vaccine design, the infant ferret model may be the key to determining the mechanisms of strain-specific imprinting in infants and the subsequent influence this established immune memory has on future infection and vaccination events.…”

Section: Influenza In the Infant And Newly Weaned Ferretmentioning

confidence: 99%

The Intersection of Age and Influenza Severity: Utility of Ferrets for Dissecting the Age-Dependent Immune Responses and Relevance to Age-Specific Vaccine Development

Rioux

Francis

Swan

et al. 2021

Viruses

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Many factors impact the host response to influenza virus infection and vaccination. Ferrets have been an indispensable reagent for influenza virus research for almost one hundred years. One of the most significant and well-known factors affecting human disease after infection is host age. Another significant factor is the virus, as strain-specific disease severity is well known. Studying age-related impacts on viral infection and vaccination outcomes requires an animal model that reflects both the physiological and immunological changes that occur with human aging, and sensitivity to differentially virulent influenza viruses. The ferret is uniquely susceptible to a plethora of influenza viruses impacting humans and has proven extremely useful in studying the clinical and immunological pictures of influenza virus infection. Moreover, ferrets developmentally have several of the age-related physiological changes that occur in humans throughout infancy, adulthood, old age, and pregnancy. In this review, we discuss ferret susceptibility to influenza viruses, summarize previous influenza studies using ferrets as models of age, and finally, highlight the application of ferret age models in the pursuit of prophylactic and therapeutic agents to address age-related influenza disease severity.

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Immune Imprinting in the Influenza Ferret Model

Cited by 12 publications

References 121 publications

N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

Host Diversity and Potential Transmission Pathways of SARS-CoV-2 at the Human-Animal Interface

The Intersection of Age and Influenza Severity: Utility of Ferrets for Dissecting the Age-Dependent Immune Responses and Relevance to Age-Specific Vaccine Development

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