Model Organisms to Verify Vaccine Against Human Diseases

Verification of vaccine efficacy is necessary as it shows how well a candidate vaccine works in humans. However, testing vaccine efficacy in humans is costly, time-consuming, and complex because it may involve a large number of participants who might have geographic or demographic biases and it requires following cohorts of subjects for years to monitor protective efficacy. Moreover, vaccine efficacy studies in humans could get trouble in ethical issues when it comes to certain pathogens like HIV. Contrarily, model organisms, which are easy to maintain and breed in a laboratory setting with a short generation time, permit faster evaluation of promising vaccine candidates at a lower cost and risk compared with humans.

Some model organisms have similar genes or similar-sized genomes to humans, which means they can mimic the pathophysiology of human disease after being infected by a target pathogen and bear a resemblance to human immune responses. Theoretically, the immune system of model organisms and humans share most underlying principles in terms of genome function. Therefore, a wide range of subjects, including virology, bacteriology, parasitology, and dermatology, take advantage of immunology antibodies generated in model organisms to verify and evaluate vaccine efficacy against human diseases.

Researchers from Yale University and the University of Pennsylvania recently published a study in Science Translational Medicine, introducing an mRNA-based vaccine that aims to prevent Lyme disease by deterring the tick itself. Lyme disease is a vector-borne disease caused by Borrelia burgdorferi, a bacterium carried and passed into the bloodstream by ticks when ticks bite human skin. A new approach was taken to develop a vaccination against Lyme disease, which is not targeting the pathogen but the tick vector. Researchers packaged 19 mRNAs, which encoded proteins expressed in tick saliva, into lipid nanoparticles and injected them into the host. mRNAs would be translated into proteins in the host, and then elicit a protective immune response through antibody generation.

In this study, researchers used guinea pigs as model organisms to verify the vaccine efficacy against Lyme disease. After the model organism was immunized with the mRNA vaccine, guinea pig antibodies against many of the selected proteins in the vaccine were generated, indicating the vaccination has elicited an immune response in the host. Compared to unvaccinated guinea pigs, vaccinated model guinea pigs appear early erythema or obvious reddening of the skin at the bite site. It's inspiring because these symptoms make it easier for 70% of people who never noticed the tick bite to identify and remove the tick from the skin before the transmission of the disease-causing bacterium. Besides, signs of tick immunity, such as tick rejection, poor tick feeding, and detachment, were also observed on the vaccinated guinea pigs.

Generally, studies using animal models have achieved varying degrees of success had in predicting therapeutics and vaccine outcomes in human studies. For instance, model organism antibodies have been widely adopted in the development of therapeutics. And in the design and evaluation of vaccines against human diseases, such as early-generation DNA vaccines and viral vector-based approaches, promising research results are yielded in animal models.