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Human Metapneumovirus (hMPV) Infection and MPV467 Treatment in Immunocompromised Cotton Rats Sigmodon hispidus
Kevin C Yim1, Jarrod J Mousa2,3, Jorge C G Blanco1
1Sigmovir Biosystems, Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Abstract:
Human metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats S. hispidus immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected S. hispidus. The efficacy of prophylactic and therapeutic administration of the anti-hMPV antibody MPV467 was also evaluated. Immunosuppressed animals had higher pulmonary and nasal titers of hMPV on day 5 post-infection compared to normal animals, and large amounts of hMPV were still present in the respiratory tract of immunosuppressed animals on days 7 and 9 post-infection, indicating prolonged viral replication. Immunosuppression was accompanied by reduced pulmonary histopathology in hMPV-infected cotton rats compared to normal animals; however, a delayed increase in pathology and pulmonary chemokine expression was seen in immunosuppressed cotton rats. Prophylactic and therapeutic MPV467 treatments protected both upper and lower respiratory tracts against hMPV infection. The lung pathology and pulmonary expression of IP-10 and MIP-1α mRNA were reduced by therapeutic MPV467 administration. These results indicate that immunosuppressed cotton rats represent a useful model for studying hMPV pathogenesis and for evaluating therapeutics that could alleviate hMPV-induced disease in immunocompromised subjects.
Insights
A new animal model using immunosuppressed cotton rats effectively mimics human metapneumovirus (hMPV) infection, showing prolonged viral replication and aiding in the evaluation of new hMPV therapeutics.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Human metapneumovirus (hMPV) causes significant respiratory illness, particularly in immunocompromised individuals.
- A suitable animal model for studying hMPV infection in immunocompromised hosts was previously lacking.
Purpose of the Study:
- To establish and characterize an immunocompromised cotton rat model for hMPV infection.
- To compare hMPV replication and pulmonary inflammation in immunosuppressed versus normal cotton rats.
- To evaluate the efficacy of the anti-hMPV antibody MPV467 in this model.
Main Methods:
- Cotton rats (S. hispidus) were immunosuppressed using cyclophosphamide.
- Both immunosuppressed and normal cotton rats were infected with hMPV.
- Viral titers, pulmonary histopathology, and chemokine expression were assessed post-infection.
- The anti-hMPV antibody MPV467 was administered prophylactically and therapeutically.
Main Results:
- Immunosuppressed rats exhibited higher pulmonary and nasal hMPV titers and prolonged viral presence.
- Delayed pulmonary inflammation and chemokine expression were observed in immunosuppressed animals.
- Both prophylactic and therapeutic MPV467 treatments effectively protected the respiratory tracts from hMPV infection.
- Therapeutic MPV467 reduced lung pathology and specific chemokine mRNA expression (IP-10, MIP-1α).
Conclusions:
- Immunosuppressed cotton rats provide a valuable model for investigating hMPV pathogenesis.
- This model is effective for evaluating therapeutic strategies against hMPV in immunocompromised populations.
- MPV467 demonstrates potential as a treatment for hMPV infections.
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