Animal Models in Modern Vaccine Development. Animal Models.
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The recognition that animals could be used as potential models for human infectious diseases dates back to Jenner, who in 1798 observed that milkmaids were resistant to smallpox because they were exposed to cattle infected with a related virus
Pasteur investigated anthrax and rabies pathogenesis in animal models
A more recent example of an animal viral disease being used to develop a platform technology for use in licensing a human vaccine are virus-like particles (VLPs) for immunization against Papillomavirus
The concept of using recombinant Papillomavirus VLPs was first established for the control of disease caused by bovine, canine and rabbitPapillomavirus, and eventually provided the basis for subsequent licensure of a bivalent and quadravalent HPV vaccine to control cervical cancer.
The development of this vaccine confirms that studies in animals remain relevant to the control of infectious diseases in humans
Humans and mice have a reasonable number of genes in common– those involved in the development of major organs and major sections of our physiology such as the nervous, muscular, skeletal, cardiovascular, immune and endocrine systems.
In addition to having many structures and functions similar to humans, mice are relatively short-lived and explosive reproducers (potentially producing a new litter every nine weeks).
So studying these animals is one of the best ways to find out how specific genes common to mammals function over generations.
This is important since it permits analysis of virulence factors and their role in invasion, penetration and toxicity, as well as the host's immune response to the pathogen
This also allows identification of specific molecules that are often required by the pathogen for infection or subsequent induction of disease and which often represent targets for the host's immune response
These gene deletions have created important animal models such as B- and T-cell-deficient mice:
Can help in vaccine development against many extra- and intracellular pathogens.
Transfer of normal or genetically modified cells from one mouse to another is being used to characterize the function of specific immune cells in the context of infection and vaccine-induced immune responses
Since many disease models in miceutilize artificial routes of challenge, in large animals however, it is often possible to use the natural route of challenge and therefore obtain more relevant correlates of immune-mediated protection
In vaccinating such population, it has frequently been observed that there are ‘low' and ‘high' responders
Utilizing an animal model that expresses the required receptors for a specific pathogen, or using natural disease models with pathology comparable to the human disease, can assist in overcoming these difficulties
For example pneumovirus (PVM) infection of mice, which has a similar pathology to respiratory syncytial virus (RSV), one of the most serious causes of respiratory illness in infants
The quality of an animal model and its appropriateness for vaccine development can be defined by its ability to reproduce relevant human physiology, which ultimately is the target population for the vaccine
Thus, good models share the same physiological characteristics, or at least reflect them as closely as possible
The physiology of the skin is very similar between humans and pigs, which renders the pig a good model for studying intracutaneous or topical delivery of the vaccine
The development of the immune system, in particular the maturation of the mucosa-associated lymphoid tissues, is similar in humans, sheep, cattle and pigs, which again makes these species good models for studying mucosal delivery of vaccines
Large animal models, such as the horse, could provide geriatric populations for the screening of a variety of possible adjuvants
Very little is known, however, regarding the functional or phenotypic changes in the immune system of most domestic species and this information will be critical to determine if these animal models are appropriate surrogates for the translation of vaccine technologies to clinical application
Third, the pathogen dose should be similar to that which would occur naturally, since it is always possible to overcome an adaptive immune response by excessive pathogen challenge or by using an unnatural route of infection
In choosing a model for respiratory infections, the structure, function and development of the respiratory tract in the animal model should resemble that of humans