New Humanized Mouse Models for COVID-19 Research



Scientists at the La Jolla Institute for Immunology (LJI), in collaboration with Synbal, Inc., have achieved a breakthrough in COVID-19 research by developing six lines of humanized mice. These mice are engineered to serve as vital models for studying human cases of COVID-19, offering invaluable insights into the virus and potential treatments.

Humanized Mouse Models: A New Frontier in COVID-19 Research

These innovative mouse models were meticulously engineered to include two critical human molecules: ACE2 and TMPRSS2. These molecules play pivotal roles in SARS-CoV-2 infection, enabling the virus to bind to and enter human cells. To ensure comprehensive insights, the models were generated on two distinct immunological backgrounds, C57BL/6 and BALB/c. This strategic approach allows researchers to delve into how these molecules contribute to infection and how the host’s genetic background influences the progression of the disease.

Epidemiologically Relevant Models for Real-World Insights

The significance of these new mouse models extends beyond their genetic makeup. They empower researchers to model SARS-CoV-2 infection and vaccination settings that mirror real-world scenarios. This epidemiological relevance is crucial for understanding how the virus spreads, evolves, and interacts with the human immune system in diverse populations. By studying various tissues at different time points following infection and/or vaccination, scientists can gain a holistic view of the disease process.

Unraveling the Immune Response to SARS-CoV-2

To understand the complex interplay between the virus and the host’s immune system, tissue samples, particularly from the lungs, were meticulously analyzed. The lungs are the primary target of SARS-CoV-2 infection in humans, making them a focal point for research. The analysis revealed clear signs of SARS-CoV-2 infection within the lungs, and importantly, it showed immune cells responding to the infection in a manner that closely resembles the human immune response. This finding underscores the reliability of these mouse models in replicating crucial aspects of human COVID-19.

Strengthening Pandemic Preparedness

The development of these humanized mouse models aligns perfectly with LJI’s mission to contribute significantly to pandemic preparedness worldwide. Recognizing the global impact of infectious diseases, LJI has made these models available to the broader COVID-19 research community. This collaborative spirit aims to accelerate research efforts and equip scientists worldwide with essential tools. These models can be instrumental in studying responses to emerging SARS-CoV-2 variants and future coronaviruses, ultimately bolstering our defenses against potential pandemics.

Future Applications: Beyond COVID-19

The implications of these mouse models extend far beyond the current COVID-19 pandemic. They hold immense promise for future pandemics involving viruses that exploit the same ACE2 receptor and/or TMPRSS2 molecule for entry into human cells. This versatility makes them invaluable assets in the fight against a wide range of viral threats. By studying how these viruses interact with human cells and the immune system, researchers can develop more effective vaccines, antiviral therapies, and other countermeasures, potentially saving countless lives in the face of future outbreaks.

These new mouse models provide a valuable tool for understanding how SARS-CoV-2 affects humans and for developing effective countermeasures against the virus.

Frequently Asked Questions

What makes these humanized mouse models unique?

These models are unique because they have been engineered to carry the human ACE2 and TMPRSS2 genes, making them susceptible to SARS-CoV-2 infection in a way that mimics human responses. They offer a more accurate representation of the virus’s behavior in humans compared to conventional mouse models.

How are these models being used to study COVID-19?

Researchers are using these models to investigate various aspects of COVID-19, including:

  • The pathogenesis of SARS-CoV-2 infection
  • The efficacy of potential vaccines and antiviral drugs
  • The long-term effects of COVID-19

Are these models available to other researchers?

Yes, LJI has made these models available to the wider research community to accelerate global efforts to combat COVID-19.

What is the significance of having different immunological backgrounds in these models?

The different immunological backgrounds (C57BL/6 and BALB/c) help researchers study how the host’s genetic makeup influences their response to SARS-CoV-2 infection. This is crucial because different individuals and populations may respond differently to the virus and to treatments.

Conclusion: A Beacon of Hope in the Fight Against COVID-19 and Future Threats

The development of these humanized mouse models marks a pivotal advancement in our understanding and ability to combat COVID-19. These models, by providing a more accurate reflection of human responses to the virus, are invaluable tools for researchers striving to develop effective vaccines, therapies, and preventive measures. As we navigate the current pandemic and prepare for future health challenges, these models offer a beacon of hope, illuminating the path toward a healthier and safer world. Their availability to the global research community underscores the importance of collaboration and open science in addressing global health crises.

Source: La Jolla Institute for Immunology


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