Cell-based passive immunization for protection against SARS-CoV-2 infection

Area of Science:

• Biotechnology
• Immunology
• Stem Cell Therapy

Background:

• Immunologically impaired individuals exhibit poor vaccine response, necessitating alternative COVID-19 protection strategies.
• Monoclonal antibodies (mAbs) offer temporary protection against SARS-CoV-2 but have a limited lifespan.
• There is a need for durable passive prophylaxis against viral infections, especially for vulnerable populations.

Purpose of the Study:

• To develop a cell therapy approach for sustained delivery of neutralizing biologics (nBios) against SARS-CoV-2.
• To engineer safe and universally accepted stem cells for long-term secretion of nBios.
• To demonstrate the potential of cell-based therapy for enduring immune protection.

Main Methods:

• Mouse embryonic stem cells were engineered with FailSafe™ and allogeneic tolerance technologies to express SARS-CoV-2 neutralizing biologics (nBios).
• Transgenic cells were transplanted into mice, and nBio levels and neutralizing activity in circulation were monitored over time.
• FailSafe™ human-induced pluripotent stem cells were similarly engineered to express SARS-CoV-2 nBios.

Main Results:

• Engineered mouse embryonic stem cells secreted functional and potent SARS-CoV-2 nBios.
• Subcutaneous transplantation resulted in long-term delivery of protective nBio titers in vivo.
• Engineered human-induced pluripotent stem cells demonstrated the capacity to secrete highly potent nBios.

Conclusions:

• Engineered stem cells secreting nBios offer a promising 'off-the-shelf' cell therapy for sustained protection.
• This approach provides a potential strategy for long-term passive immunity against SARS-CoV-2 and future viral threats.
• Cellular delivery of neutralizing antibodies presents a viable alternative to conventional antibody therapies for viral prophylaxis.