Preclinical models that recapitulate aspects of human airway disease are essential for advancing new therapies and vaccines. In the current study published in the journal mBIOthe researchers at Baylor College of Medicine iThey report the development of a versatile human nose organoid: a laboratory representation of the cells lining the inside of the nose where the first events of a natural viral infection take place.
The model also proved to be a useful tool for testing the efficacy of treatments.
Using nasal organoids, which model the complex interactions between human cells and the virus. The team showed key differences between infection with SARS-CoV-2, the virus that causes COVID-19, and that of respiratory syncytial virus (RSV). An important pediatric respiratory virus, providing a better understanding of the early steps towards the disease and leading to potential new therapies.
The model also proved to be a useful tool for testing the efficacy of treatments such as palivizumab. An FDA-approved monoclonal antibody to prevent severe RSV disease in high-risk infants.
The organoid system of the human nose is part of the preclinical evaluation of therapies that would help speed the transfer of therapies developed in the laboratory to the bedside.
“The human nose organoids we have developed provide access to the interior of the human nose. This allows us to study the first events of the infection in the laboratory. Something we hadn’t had before. We have successfully grown human nose organoids from both adults and babies.”
The researchers simulated a natural infection
To study the interaction between SARS-CoV-2 or RSV and the epithelium of the nose, the researchers simulated a natural infection. Placing each virus separately on the air side of culture plates and studying the changes that occurred in the organoid of the nose.
The team also used their human nose organoid model of RSV infection to test the efficacy of palivizumab. In this case, they placed the therapeutic monoclonal antibody in the fluid-filled chamber. This, to more closely resemble the human experience where therapeutic antibodies enter the bloodstream and provide protection to the respiratory tract against RSV infection.
“In our model, palivizumab effectively prevented RSV infection in a concentration-dependent manner,” said Avadhanula, co-director of the Certified Respiratory Virus Diagnostic Laboratory (CLIA) and the laboratory’s research program.
For the first time, the team described a noninvasive approach
In this study, for the first time, the team described a noninvasive, reproducible, and reliable approach to establishing human nose organoids that would allow long-term studies. Previous models were produced by invasive lung or nose biopsy or bronchoalveolar lavage.
“The ease of obtaining nasal swab samples facilitates our noninvasive approach in the general adult population, as well as in the vulnerable pediatric population,” Piedra said.
Another advantage of using this novel human nose organoid system is that it can reveal how the initial control of a person’s infection occurs. As well as providing information about what would make one person more susceptible to a virus than another.
This system can also be used to study other respiratory viruses and potentially other disease-causing microbes.
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