Immunoengineering Trainee Seminar

Carolina Colon and Augustine Duffy presenting

Presentation #1

"Cell Therapies for Astronauts: How Advancing the Field of CAR-T Cell Therapy using a Microfluidic-based Delivery can Provide the Tools for Long-term Space Exploration"

Carolina Colón, Ph.D. Graduate Student, Bioengineering - Advisors: Todd Sulchek, Ph.D., Jud Ready, Ph.D.

In the challenging environment of outer space, personalized cellular therapies, such as Chimeric Antigen Receptor (CAR) T cells, offer a groundbreaking solution for astronaut health. First approved by the FDA in 2017, these therapies have shown exceptional results in treating cancers and hematological conditions by genetically modifying a person's cells to fight specific diseases. Such tailored treatments provide a robust medical toolkit, equipping astronauts to face the harsh conditions of space for extended periods with a fleet of microscopic caretakers within their bodies.

Advancements in technology, including the use of microfluidics and delivery through mechanoporation—a technique that preserves cell physiology—enhance the manufacturing process, making these therapies more affordable and accessible. As production becomes more streamlined, cell therapies could address a wide range of health issues during space missions, from combating immunological diseases to regenerating bone and tissue, thereby extending mission durations and supporting long-term habitation on other celestial bodies. By pushing the boundaries of space travel, these cellular therapies not only promise to safeguard astronaut health but also hold the potential for revolutionary healthcare benefits on Earth.

Presentation #2

Augustine Duffy, Ph.D. Graduate Student

"Broad Protection Against Clade 1 Sarbecoviruses After a Single Immunization with Cocktail Spike-protein-nanoparticle Vaccine"

Since the turn of the century, three betacoronaviruses have caused outbreaks of severe disease in humans, two of which – SARS-CoV-1 and SARS-CoV-2 – are closely related and use the same receptor. Effective SARS-CoV-2 vaccines have been developed to address the COVID-19 pandemic, but the continual emergence of immune evasive SARS-CoV-2 variants has required formulations to be updated routinely. Here, we sought to create a cocktail vaccine broad enough to protect against both SARS-CoV-1-like and SARS-CoV-2-like coronaviruses while minimizing the number of different antigens. We first immunized hamsters with monovalent vaccine formulations using our spike protein nanoparticle platform. Immunization with spike protein from SARS-CoV-2 variants completely protected hamsters from BA.5 challenge while vaccines formulated with SARS-CoV-1 spike or SARS-CoV-1-like SHC014 spike provided no protection. Neutralization showed similar patterns, with SARS-CoV-1-like vaccines in particular only eliciting neutralizing antibodies against SARS-CoV-1-like viruses

We then used antigenic cartography based on this neutralization data to choose antigens for bivalent and trivalent vaccine formulations. These cocktail vaccines completely protected female hamsters against BA.5 and XBB.1 challenges with no detectable virus in the lungs. The trivalent cocktails elicited highly neutralizing responses against all tested SARS-CoV-2 variants and the SARS-CoV-1-like bat coronaviruses SHC014 and WIV1. Finally, our 614D/SHC014/XBB trivalent spike formulation completely protected human ACE2-transgenic female hamsters against challenges with WIV1 and SHC014 with no detectable virus in the lungs. Collectively, these results illustrate that our trivalent protein-nanoparticle cocktail can provide broad protection against SARS-CoV-2-like and SARS-CoV-1-like coronaviruses.

Reference: Halfmann*, Loeffler*, Duffy* et al. Nature Communications 15 (2024), 1284.

*Co-first authors

The Immunoengineering Training Seminar Series is supported by the Center for Immunoengineering at Georgia Tech