Q.Why are transgenic animals particularly valuable for testing the safety of a vaccine before it is used on humans, compared to testing directly on non-transgenic animals?

[!TLDR] Transgenic animals can be engineered to be susceptible to a specific pathogen (unlike an ordinary animal that might naturally resist it), giving a realistic living model in which a candidate vaccine's safety and effectiveness against that exact pathogen can be tested. …

Testing whether a new vaccine is safe and effective requires exposing a living organism to the actual target pathogen (or a carefully controlled form of it) after vaccination, and observing whether the vaccinated organism is protected without suffering unacceptable side effects. This kind of testing must be carried out in animals first, well before any human clinical trial is considered, precisely to establish a reasonable degree of safety before ever exposing a human volunteer to the vaccine.

The difficulty is that many pathogens that infect and cause disease in humans do not naturally infect other species, including ordinary, non-transgenic mice; a normal mouse's immune system and cellular biology may simply be resistant to that particular pathogen, meaning the pathogen cannot properly establish an infection in that mouse at all. Testing a candidate vaccine in such a naturally resistant animal would not give a meaningful result, because the animal was never actually at risk of the disease that the vaccine is meant to protect against. …

Explain the core problem first (many pathogens do not naturally infect ordinary lab animals), then explain how enginee …

Do not say ordinary (non-transgenic) animals simply cannot be used for ANY vaccine testing -- the specific issue is testing against pathogens that particular ordinary anima …