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Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection
Hadas Tamir1, Sharon Melamed1, Noam Erez1
1Department of Infectious Diseases, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 7410001, Israel.
Abstract:
SARS-CoV-2, a member of the coronavirus family, is the causative agent of the COVID-19 pandemic. Currently, there is still an urgent need in developing an efficient therapeutic intervention. In this study, we aimed at evaluating the therapeutic effect of a single intranasal treatment of the TLR3/MDA5 synthetic agonist Poly(I:C) against a lethal dose of SARS-CoV-2 in K18-hACE2 transgenic mice. We demonstrate here that early Poly(I:C) treatment acts synergistically with SARS-CoV-2 to induce an intense, immediate and transient upregulation of innate immunity-related genes in lungs. This effect is accompanied by viral load reduction, lung and brain cytokine storms prevention and increased levels of macrophages and NK cells, resulting in 83% mice survival, concomitantly with long-term immunization. Thus, priming the lung innate immunity by Poly(I:C) or alike may provide an immediate, efficient and safe protective measure against SARS-CoV-2 infection.
Insights
Intranasal Poly(I:C) treatment boosts innate immunity against SARS-CoV-2 in mice. This early intervention reduced viral load, prevented cytokine storms, and increased survival, offering a potential therapeutic strategy for COVID-19.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) causes the ongoing COVID-19 pandemic.
- There is a critical need for effective therapeutic interventions against SARS-CoV-2.
Purpose of the Study:
- To evaluate the therapeutic potential of intranasal Poly(I:C) against a lethal SARS-CoV-2 challenge.
- To investigate the effects of Poly(I:C) on innate immunity, viral load, and survival in a mouse model.
Main Methods:
- K18-hACE2 transgenic mice were treated intranasally with the synthetic TLR3/MDA5 agonist Poly(I:C) before infection with a lethal dose of SARS-CoV-2.
- Gene expression, viral load, immune cell populations, and survival rates were assessed.
Main Results:
- Early Poly(I:C) treatment synergistically upregulated innate immunity genes in the lungs.
- Significant reduction in viral load, prevention of lung and brain cytokine storms, and increased macrophage and NK cell levels were observed.
- An 83% survival rate was achieved, along with evidence of long-term immunization.
Conclusions:
- Priming lung innate immunity with Poly(I:C) offers an immediate, efficient, and safe protective strategy against SARS-CoV-2 infection.
- Intranasal Poly(I:C) demonstrates significant therapeutic efficacy in a preclinical model of COVID-19.
