Animal Models for Influenza Research: Strengths and Weaknesses

Abstract

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.

Influenza antivirals and animal models

“…Golden Syrian hamsters (GSH; Mesocricetus auratus ) are naturally susceptible to a wide range of IAV subtypes including H1N1, H2N2, H3N2, H5N1, and H9N2 and IBV (Fig. 2) [92]. Intranasal inoculation is the most common infection route, but intragastric inoculation of H5N1 and aerosol transmission of pandemic H1N1 and seasonal H3N2 IAV have also been reported in GSH [120,121].…”

“…Guinea pigs, most commonly the Hartley strain, are utilized as an animal model for influenza research (Fig. 2) [92]. Comparable to golden Syrian hamsters and cotton rats, guinea pigs are susceptible to influenza viruses without prior adaptation, are easier to handle, and possess relatively inexpensive maintenance costs.…”

Airborne Transmission of Avian Origin H9N2 Influenza A Viruses in Mammals

“…Reassortment between avian and mammalian influenza viruses has led to the emergence of pandemic viruses in the past. Transmission studies designed to evaluate the potential of IAV transmission in mammals are commonly performed in ferrets, which present similar characteristics for IAV infection as humans in terms of lung pathology, clinical signs, pathogenesis, and immunity [119,120]. Wan and collaborators evaluated the replication and transmission capabilities of different H9N2 IAV isolated from avian species between 1988 and 2003, using the ferret model [71].…”

Replacement Strategies for Animal Studies in Inhalation Testing

“…Ferrets recapitulate the illness and animals can be infected with a broad range of human, avian, and porcine strains. Ferrets, guinea pigs and hamsters are suitable for vaccine testing [55]. Pigs can naturally be infected and are, therefore, the model of choice.…”