In a stunning leap for medical science, researchers have engineered a special mouse that is a near-perfect mimic of the human immune system. By giving the mice a simple, yet powerful, hormone—estrogen—they were able to create an animal model that could change how we develop new vaccines and treatments for diseases like lupus. This breakthrough could one day reduce the need for testing on non-human primates and other animals.
A New Era for Medical Research
For decades, scientists have tried to create animal models that can act as a stand-in for human research. A common approach is to create a “humanized mouse,” which is a mouse that has been given human cells and tissues. Previous humanized mice, however, were limited in their ability to model human immunity, especially when it came to developing a full, mature antibody response. These models were helpful, but they lacked the complexity and precision of a real human immune system.
A team at the University of Texas Health Science Center at San Antonio set out to overcome these limitations. They started with a special strain of mice and injected them with human cord blood cells, the building blocks of the human immune system. Here’s where their approach gets interesting: they then gave the mice a potent form of the hormone estrogen in their drinking water. This hormonal boost helped the newly introduced human cells mature and differentiate into all the specialized cells needed for a fully functional immune system.
The results were remarkable. The “super-humanized” mice, which the researchers call “THX mice,” developed a complete human immune system. They produced their own human B cells and T cells—two key players in the immune response—in their lymph nodes and other organs. The mice even developed Peyer’s patches, clusters of immune cells in the small intestine that are crucial for defending against gut infections. Another important finding was that the mice also had a human-like gut microbiome, the complex community of bacteria in our intestines that is a major part of our immune system.
A Mouse That Fights Like a Human
To see if their new immune system could actually do its job, the team gave the mice vaccines. When the THX mice were given the Pfizer-BioNTech COVID-19 mRNA vaccine, their bodies mounted a strong neutralizing antibody response. This is a massive step forward, as it means scientists can now use this model to accurately test human vaccines and treatments without having to rely on less accurate animal models. The researchers also found that the THX mice were susceptible to developing a disease that mimics human lupus, an autoimmune disorder where the body’s immune system mistakenly attacks its own tissues. This demonstrates the model’s value not just for vaccines, but for studying complex diseases as well.
What This Means for You
This discovery is a major leap forward for medical science. By using a mouse with a fully functional human immune system, researchers can now study diseases and treatments in a way that was previously only possible in humans. The ability of the THX mouse to develop mature, high-quality antibody responses to a real-world vaccine, and to develop a complex disease like lupus, positions it as an invaluable tool for future research. This new model is a major step toward creating more effective, targeted therapies and ultimately, making us all healthier.
Paper Summary
Methodology
Researchers created a new humanized mouse model, called the THX mouse, by injecting human umbilical cord blood cells (specifically CD34+ cells) into newborn mice with a genetic mutation that cleared space in their bone marrow for the human cells to grow. The mice were then given the hormone 17ß-estradiol (estrogen) in their drinking water, which helped the human immune system cells mature and differentiate. Both male and female mice were used in the study.
Results
The THX mice successfully developed a full and functional human immune system, including a human-like gut microbiome. The mice were able to produce mature antibody responses to the Pfizer-BioNTech COVID-19 mRNA vaccine and were susceptible to a disease that mimics human lupus.
Limitations
While the THX model overcomes many of the limitations of previous humanized mice, the study notes that the THX mice had few human red blood cells.
Funding and Disclosures
The researchers are affiliated with The University of Texas Health Science Center at San Antonio, and some authors have affiliations with private companies. The Pfizer COVID-19 mRNA vaccine used in the study was obtained from “discarded” vials at the university’s vaccination facility.
Publication Information
Paper Title: “A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses” Authors: Daniel P. Chupp, Carlos E. Rivera, Yulai Zhou, Yijiang Xu, Patrick S. Ramsey, Zhenming Xu, Hong Zan, and Paolo Casali Journal: Nature Immunology Published: Online on June 25, 2024, and in the August 2024 issue (Volume 25) DOI: 10.1038/s41590-024-01880-3
