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<p>Vaccines prevent the incidence of new infections, but availability of interventions that can prevent transition to severe disease is limited. Interferons (IFN) serve an important part of anti-viral host immune defense. Viruses including SARS-CoV-2 dysregulate IFN kinetics, leading to pathogenesis. The efficacy of systemically infused IFNs as a viable antiviral intervention is compromised by their adverse side effects and restrict the acceptable dosage levels. To address this problem, CD4 T cells have been engineered into a cell-based delivery platform that synthesizes antiviral IFNs upon recognizing the envelope protein of SARS-CoV-2<i>.</i> This pathway cannot be disrupted by viruses and delivers the IFNs directly where needed, reducing side effects. Prophylactic and therapeutic effects of the type-I and type-III IFNs, produced from the T-cell delivery platform, on SARS-CoV-2-infected host cells have been determined. Among the tested interferons, type-I IFN-β consistently exhibited the strongest antiviral activity. The platform is based on CD4 T cells engineered with chimeric antigen receptors and can be rapidly re-engineered for targeting any new pathogen with sensitivity toward IFNs.</p>

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CD4 T-cell platform for delivering interferons as an antiviral countermeasure with a focus on SARS-CoV-2

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月28日

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  • Xiaohe Liu,
  • Marvin A. Ssemadaali,
  • Harikrishnan Radhakrishnan,
  • Juan Arredondo,
  • Harold S. Javitz,
  • Satya Dandekar,
  • Parijat Bhatnagar

摘要

Vaccines prevent the incidence of new infections, but availability of interventions that can prevent transition to severe disease is limited. Interferons (IFN) serve an important part of anti-viral host immune defense. Viruses including SARS-CoV-2 dysregulate IFN kinetics, leading to pathogenesis. The efficacy of systemically infused IFNs as a viable antiviral intervention is compromised by their adverse side effects and restrict the acceptable dosage levels. To address this problem, CD4 T cells have been engineered into a cell-based delivery platform that synthesizes antiviral IFNs upon recognizing the envelope protein of SARS-CoV-2. This pathway cannot be disrupted by viruses and delivers the IFNs directly where needed, reducing side effects. Prophylactic and therapeutic effects of the type-I and type-III IFNs, produced from the T-cell delivery platform, on SARS-CoV-2-infected host cells have been determined. Among the tested interferons, type-I IFN-β consistently exhibited the strongest antiviral activity. The platform is based on CD4 T cells engineered with chimeric antigen receptors and can be rapidly re-engineered for targeting any new pathogen with sensitivity toward IFNs.