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Pathogens
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Animal Models of Infectious Disease
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Animal Models of Infectious Disease

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 18108

Special Issue Editor

Dr. Jason E. Comer

E-Mail Website
Guest Editor
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Interests: evaluating the efficacy of medical countermeasures against bacterial and viral agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Animal models of infectious disease have been instrumental in the advancement of human and veterinary medicine and will continue to be in the future. These models have been used in the development of new antibiotics and antivirals as well as in vaccines for new emerging diseases. With the advent of the FDA’s Animal Rule, appropriate animal models can be used as a surrogate when human clinical efficacy trials are not feasible.  For this Special Issue of Pathogens, we invite you to submit research articles, review articles, and short notes highlighting the importance of animal models in infectious disease research and/or describing new models of viral, bacterial, and parasite infections.

Prof. Jason E. Comer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal models
  • infectious disease
  • natural history studies

Published Papers (6 papers)

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Research

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20 pages, 1727 KiB  
Article
Transplacental Antibody Transfer of Respiratory Syncytial Virus Specific IgG in Non-Human Primate Mother-Infant Pairs
by Michael P. Citron, Jessica McAnulty, Cheryl Callahan, Walter Knapp, Jane Fontenot, Pablo Morales, Jessica A. Flynn, Cameron M. Douglas and Amy S. Espeseth
Pathogens 2021, 10(11), 1441; https://doi.org/10.3390/pathogens10111441 - 5 Nov 2021
Cited by 4 | Viewed by 2420
Abstract
One approach to protect new-borns against respiratory syncytial virus (RSV) is to vaccinate pregnant women in the last trimester of pregnancy. The boosting of circulating antibodies which can be transferred to the foetus would offer immune protection against the virus and ultimately the [...] Read more.
One approach to protect new-borns against respiratory syncytial virus (RSV) is to vaccinate pregnant women in the last trimester of pregnancy. The boosting of circulating antibodies which can be transferred to the foetus would offer immune protection against the virus and ultimately the disease. Since non-human primates (NHPs) have similar reproductive anatomy, physiology, and antibody architecture and kinetics to humans, we utilized this preclinical species to evaluate maternal immunization (MI) using an RSV F subunit vaccine. Three species of NHPs known for their ability to be infected with human RSV in experimental challenge studies were tested for RSV-specific antibodies. African green monkeys had the highest overall antibody levels of the old-world monkeys evaluated and they gave birth to offspring with anti-RSV titers that were proportional to their mother. These higher overall antibody levels are associated with greater durability found in their offspring. Immunization of RSV seropositive AGMs during late pregnancy boosts RSV titers, which consequentially results in significantly higher titers in the vaccinated new-borns compared to the new-borns of unvaccinated mothers. These findings, accomplished in small treatment group sizes, demonstrate a model that provides an efficient, resource sparing and translatable preclinical in vivo system for evaluating vaccine candidates for maternal immunization. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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10 pages, 9417 KiB  
Communication
Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection
by Theodor Chitlaru, Erez Bar-Haim, Liat Bar-On, Shahar Rotem, Hila Cohen, Uri Elia, David Gur, Moshe Aftalion, Ron Alkalay, Efi Makdasi, Yentl Evgy, Reut Falach, Ma’ayan Israeli, Adi Bercovich-Kinori, Hagit Achdout, Yfat Yahalom-Ronen, Ronit Rosenfeld and Ofer Cohen
Pathogens 2021, 10(8), 940; https://doi.org/10.3390/pathogens10080940 - 26 Jul 2021
Cited by 1 | Viewed by 2072
Abstract
HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was [...] Read more.
HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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17 pages, 2529 KiB  
Article
Mucosal Challenge Ferret Models of Ebola Virus Disease
by Trevor Brasel, Jason E. Comer, Shane Massey, Jeanon Smith, Jennifer Smith, Matthew Hyde, Andrew Kocsis, Melicia Gainey, Nancy Niemuth, Cheryl Triplett and Thomas Rudge, Jr.
Pathogens 2021, 10(3), 292; https://doi.org/10.3390/pathogens10030292 - 4 Mar 2021
Cited by 5 | Viewed by 1982
Abstract
Recent studies have shown the domestic ferret (Mustela putorius furo) to be a promising small animal model for the study of Ebola virus (EBOV) disease and medical countermeasure evaluation. To date, most studies have focused on traditional challenge routes, predominantly intramuscular [...] Read more.
Recent studies have shown the domestic ferret (Mustela putorius furo) to be a promising small animal model for the study of Ebola virus (EBOV) disease and medical countermeasure evaluation. To date, most studies have focused on traditional challenge routes, predominantly intramuscular and intranasal administration. Here, we present results from a non-clinical pathogenicity study examining oronasal, oral, and ocular mucosal challenge routes in ferrets. Animals were challenged with 1, 10, or 100 plaque forming units EBOV followed by monitoring of disease progression and biosampling. Ferrets administered virus via oronasal and oral routes met euthanasia criteria due to advanced disease 5–10 days post-challenge. Conversely, all ferrets dosed via the ocular route survived until the scheduled study termination 28-day post-challenge. In animals that succumbed to disease, a dose/route response was not observed; increases in disease severity, febrile responses, serum and tissue viral load, alterations in clinical pathology, and gross/histopathology findings were similar between subjects. Disease progression in ferrets challenged via ocular administration was unremarkable throughout the study period. Results from this study further support the ferret as a model for EBOV disease following oral and nasal mucosa exposure. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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18 pages, 2114 KiB  
Article
The Impact of Age and Sex on Mouse Models of Melioidosis
by Christopher P. Klimko, Sylvia R. Treviño, Alicia M. Moreau, Michael J. Aponte Cuadrado, Joshua R. Meyer, David P. Fetterer, Susan L. Welkos, Patricia L. Worsham, Norman Kreiselmeier, Carl Soffler and Christopher K. Cote
Pathogens 2020, 9(2), 113; https://doi.org/10.3390/pathogens9020113 - 11 Feb 2020
Cited by 5 | Viewed by 3067
Abstract
Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse [...] Read more.
Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB/c mice develop an acute infection with B. pseudomallei, whereas the C57BL/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD50 of the B. pseudomallei K96243 strain in both female and male BALB/c and C57BL/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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Review

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22 pages, 2350 KiB  
Review
Galleria mellonella as a Good Model to Study Acinetobacter baumannii Pathogenesis
by Ye Tao, Luminita Duma and Yannick Rossez
Pathogens 2021, 10(11), 1483; https://doi.org/10.3390/pathogens10111483 - 14 Nov 2021
Cited by 22 | Viewed by 3798
Abstract
The invertebrate model, Galleria mellonella, has been widely used to study host–pathogen interactions due to its cheapness, ease of handling, and similar mammalian innate immune system. G. mellonella larvae have been proven to be useful and a reliable model for analyzing pathogenesis [...] Read more.
The invertebrate model, Galleria mellonella, has been widely used to study host–pathogen interactions due to its cheapness, ease of handling, and similar mammalian innate immune system. G. mellonella larvae have been proven to be useful and a reliable model for analyzing pathogenesis mechanisms of multidrug resistant Acinetobacter baumannii, an opportunistic pathogen difficult to kill. This review describes the detailed experimental design of G. mellonella/A. baumannii models, and provides a comprehensive comparison of various virulence factors and therapy strategies using the G. mellonella host. These investigations highlight the importance of this host–pathogen model for in vivo pathogen virulence studies. On the long term, further development of the G. mellonella/A. baumannii model will offer promising insights for clinical treatments of A. baumannii infection. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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17 pages, 732 KiB  
Review
Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys
by Nor Azila Muhammad Azami, Tomohiko Takasaki, Ichiro Kurane and Meng Ling Moi
Pathogens 2020, 9(4), 247; https://doi.org/10.3390/pathogens9040247 - 27 Mar 2020
Cited by 13 | Viewed by 3329
Abstract
Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, [...] Read more.
Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. Preclinical studies in vaccine development usually include parameters such as safety evaluation, induction of viremia and antigenemia, immunogenicity, and vaccine effectiveness. Although mice have been used as a model, non-human primates have an advantage over mice because of their relative similarity to humans in their genetic composition and immune responses. This review compares the viremia kinetics and antibody responses of cynomolgus macaques (Macaca fasicularis), common marmosets (Callithrix jacchus), and tamarins (Saguinus midas and Saguinus labitus) and summarize the perspectives and the usefulness along with challenges in dengue vaccine development. Full article
(This article belongs to the Special Issue Animal Models of Infectious Disease)
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