September 25, 2026
Advagene's New Drug Demonstrates Potential Against SARS-CoV-2: 《Journal of Microbiology, Immunology and Infection》Publication Highlights Mucosal Immunity and Lung Protection
- Background and Challenges:
- Acute respiratory viral infections (such as SARS-CoV-2) remain a major global health burden.
- Current intramuscular vaccines have a limited capacity to induce mucosal immunity at the respiratory epithelium—the primary site of viral entry.
- This study evaluated whether LTh(αK), a detoxified adjuvant with an established safety profile, can act as a mucosal immunomodulator to enhance immunity and mitigate respiratory tract injury.
- Experimental Design and Methods:
- As a Vaccine Adjuvant (Mouse Model): Mice were intranasally administered the SARS-CoV-2 spike protein (S2P) vaccine adjuvanted with LTh(αK). Changes in serum antibodies (IgG, IgA) and cytokines were then analyzed.
- As an Immunotherapy (Syrian Hamster Model): Following SARS-CoV-2 infection, hamsters were treated with intranasal LTh(αK). Clinical parameters, viral loads, histopathology, and cytokine transcription were assessed.
- Key Findings:
- Enhanced Humoral Immune Response: As an adjuvant, LTh(αK) significantly increased SARS-CoV-2 spike-specific serum IgG and IgA levels.
- Promoted Th1/Th2 Immune Balance: LTh(αK) effectively elevated the expression of both Th1 and Th2 cytokines, demonstrating its potent immunomodulatory capabilities.
- Attenuated Clinical Symptoms and Early Lung Injury: As an immunotherapeutic agent, LTh(αK) alleviated infection-induced symptoms, such as hypothermia. On day 3 post-infection, the overall histopathological lesion score in the treatment group was significantly lower.
- Stimulated Interferon and Cytoprotective Mechanisms: LTh(αK) significantly increased interferon-beta (IFNβ) transcription in the cranial lung lobe. Ultrastructural examinations showed that it promoted monocyte activation while reducing mucin production, hemorrhage, and the destruction of the lung parenchyma.
- Host-Directed Mechanism of Action: LTh(αK) did not significantly reduce viral titers at any time point, indicating that it mitigates tissue injury by modulating the host's immune response rather than directly clearing the virus.
- Research Conclusions:
- LTh(αK) enhances balanced humoral immunity (including serum IgA) and effectively attenuates early lung injury.
- These proof-of-concept findings support LTh(αK) as a highly promising candidate for a "mucosal immunomodulator" against acute respiratory viral infections, showcasing significant clinical translational potential.
Journal Link: https://www.sciencedirect.com/science/article/pii/S168411822600126X
