State-of-the-art preclinical evaluation of COVID-19 vaccine candidates

The coronavirus disease 2019 (COVID-19) results from the infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and primarily affects the respiratory tissue. Since first reported from Wuhan, China in December 2019, the virus has resulted in an unprecedented pandemic. Vaccination against SARS-CoV-2 can control the further spread of the ongoing pandemic by making people immunised to SARS-CoV-2. Several vaccines have been approved for use in clinics, a lot many are in different stages of development. Diligent interpretations from the preclinical evaluation are crucial to identify the most effective and safest vaccine candidates. Multiple vaccine candidates/variants have been tested in small animal models with relative ease and further in non-human primate models before being taken into clinical development. Here, we review the state-of-the-art strategies employed for a thorough preclinical evaluation of COVID-19 vaccine candidates. We summarise the methods in place to identify indicators which make the vaccine candidate effective in controlling SARS-CoV-2 infection and/or COVID-19 and are safe for administration as inferred by their (1) biophysical/functional attributes (antigen expression, organization, functionality, and stability); (2) immunogenicity in animal models and protective correlates [SARS-CoV-2 specific binding/neutralising immunoglobulin titer, B/T-cell profiling, balanced T-helper type-1 (Th1) or type-2 (Th2) response (Th1:Th2), and anamnestic response]; (3) protective correlates as interpreted by controlled pathology of the respiratory tissue (pulmonary clinical and immunopathology); and finally, (4) strategies to monitor adverse effects of the vaccine candidates.

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COVID-19 Basics and Vaccine Development with a Canadian Perspective

Canadian Journal of Microbiology ◽

10.1139/cjm-2020-0421 ◽

2020 ◽

Author(s):

Marina Liu ◽

Xiongbiao Chen

Keyword(s):

Animal Models ◽

Severe Acute Respiratory Syndrome ◽

Clinical Evaluation ◽

Vaccine Development ◽

Specific Treatment ◽

Vaccine Candidates ◽

Preclinical Evaluation ◽

Canadian Perspective ◽

Basic Biology

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of July 31, 2020, there are at least 139 vaccine candidates from around the globe are in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada.

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Vaccine Development for Severe Fever with Thrombocytopenia Syndrome

Viruses ◽

10.3390/v13040627 ◽

2021 ◽

Vol 13 (4) ◽

pp. 627

Author(s):

Tomoki Yoshikawa

Keyword(s):

Animal Models ◽

Vaccine Development ◽

Viral Vector ◽

Case Fatality ◽

Small Animal ◽

Primate Model ◽

Hamster Model ◽

Vaccine Candidates ◽

Cat Model ◽

Severe Fever

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.

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A stepping stone to enable preclinical evaluation of multimodal thin-film probes in small animal models

2021 10th International IEEE/EMBS Conference on Neural Engineering (NER) ◽

10.1109/ner49283.2021.9441332 ◽

2021 ◽

Author(s):

Danesh Ashouri Vajari ◽

Maria Vomero ◽

Volker A. Coenen ◽

Thomas Stieglitz

Keyword(s):

Thin Film ◽

Animal Models ◽

Small Animal ◽

Stepping Stone ◽

Preclinical Evaluation ◽

Small Animal Models

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Animal Models for Salmonellosis: Applications in Vaccine Research

Clinical and Vaccine Immunology ◽

10.1128/cvi.00258-16 ◽

2016 ◽

Vol 23 (9) ◽

pp. 746-756 ◽

Cited By ~ 18

Author(s):

Ellen E. Higginson ◽

Raphael Simon ◽

Sharon M. Tennant

Keyword(s):

Animal Models ◽

Human Disease ◽

Vaccine Development ◽

Clinical Testing ◽

Vaccine Research ◽

Content Type ◽

Vaccine Candidates ◽

Preclinical Evaluation ◽

Advantages And Disadvantages ◽

The Right

ABSTRACTSalmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines forSalmonella entericaserovar Typhi, these vaccines are generally ineffective against otherSalmonellaserovars. Vaccines that target paratyphoid and nontyphoidalSalmonellaserovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for variousSalmonellaserovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models forSalmonellainfection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.

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Molecular and Cellular Mechanisms Underlying Temperature-Dependent Sex Determination in Turtles

Sexual Development ◽

10.1159/000515296 ◽

2021 ◽

pp. 1-9

Author(s):

Horacio Merchant-Larios ◽

Verónica Díaz-Hernández ◽

Diego Cortez

Keyword(s):

Animal Models ◽

Sex Determination ◽

Incubation Temperature ◽

State Of The Art ◽

Current Understanding ◽

Temperature Dependent ◽

Cellular Mechanisms ◽

Male Phenotype ◽

History Of ◽

Reptilian Species

The discovery in mammals that fetal testes are required in order to develop the male phenotype inspired research efforts to elucidate the mechanisms underlying gonadal sex determination and differentiation in vertebrates. A pioneer work in 1966 that demonstrated the influence of incubation temperature on sexual phenotype in some reptilian species triggered great interest in the environment’s role as a modulator of plasticity in sex determination. Several chelonian species have been used as animal models to test hypotheses concerning the mechanisms involved in temperature-dependent sex determination (TSD). This brief review intends to outline the history of scientific efforts that corroborate our current understanding of the state-of-the-art in TSD using chelonian species as a reference.

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Placental hypoxia: What Have we Learnt from Small Animal Models?

Placenta ◽

10.1016/j.placenta.2021.03.018 ◽

2021 ◽

Author(s):

Emma Siragher ◽

Amanda N. Sferruzzi-Perri

Keyword(s):

Animal Models ◽

Small Animal ◽

Small Animal Models

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Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0022 ◽

2017 ◽

Vol 28 (1) ◽

pp. 31-43 ◽

Cited By ~ 12

Author(s):

Lan Huang ◽

Fengyan Zhao ◽

Yi Qu ◽

Li Zhang ◽

Yan Wang ◽

...

Keyword(s):

Animal Models ◽

Small Animal ◽

Underlying Disease ◽

Therapeutic Interventions ◽

Hypoxic Ischemic Encephalopathy ◽

Large Animal ◽

Large Animal Models ◽

Neurological Research ◽

Serious Disease ◽

Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

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Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible to Monkeypox Virus Infection for Use as Small Animal Models

Journal of Virology ◽

10.1128/jvi.00621-10 ◽

2010 ◽

Vol 84 (16) ◽

pp. 8172-8180 ◽

Cited By ~ 43

Author(s):

Jeffrey L. Americo ◽

Bernard Moss ◽

Patricia L. Earl

Keyword(s):

Animal Models ◽

B Lymphocyte ◽

Inbred Mouse ◽

Lethal Dose ◽

Small Animal ◽

Congo Basin ◽

Mouse Strains ◽

Dependent Manner ◽

Inbred Mouse Strains ◽

Monkeypox Virus

ABSTRACT Infection with monkeypox virus (MPXV) causes disease manifestations in humans that are similar, although usually less severe, than those of smallpox. Since routine vaccination for smallpox ceased more than 30 years ago, there is concern that MPXV could be used for bioterrorism. Thus, there is a need to develop animal models to study MPXV infection. Accordingly, we screened 38 inbred mouse strains for susceptibility to MPXV. Three highly susceptible wild-derived inbred strains were identified, of which CAST/EiJ was further developed as a model. Using an intranasal route of infection with an isolate of the Congo Basin clade of MPXV, CAST/EiJ mice exhibited weight loss, morbidity, and death in a dose-dependent manner with a calculated 50% lethal dose (LD50) of 680 PFU, whereas there were no deaths of BALB/c mice at a 10,000-fold higher dose. CAST/EiJ mice exhibited greater MPXV sensitivity when infected via the intraperitoneal route, with an LD50 of 14 PFU. Both routes resulted in MPXV replication in the lung, spleen, and liver. Intranasal infection with an isolate of the less-pathogenic West African clade yielded an LD50 of 7,600 PFU. The immune competence of CAST/EiJ mice was established by immunization with vaccinia virus, which induced antigen-specific T- and B-lymphocyte responses and fully protected mice from lethal doses of MPXV. The new mouse model has the following advantages for studying pathogenesis of MPXV, as well as for evaluation of potential vaccines and therapeutics: relative sensitivity to MPXV through multiple routes, genetic homogeneity, available immunological reagents, and commercial production.

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