Innovative Cell-Free Technique Accelerates Nipah Vaccine Development

Researchers at Cornell University and Northwestern University have unveiled a groundbreaking, cell-free method for rapidly assembling nanoparticle vaccines that mimic viruses at the molecular level. This novel approach, detailed in the study titled "Cell-Free Expression of Nipah Virus Transmembrane Proteins for Proteoliposome Vaccine Design," published on June 3, 2025, in the journal ACS Nano, has the potential to significantly expedite vaccine development for deadly viruses, including Nipah, which has a fatality rate that can reach 75% and currently lacks approved therapies or vaccines.

The research team, led by Susan Daniel, the William C. Hooey Director of the R.F. Smith School of Chemical and Biomolecular Engineering at Cornell, along with Hector Aguilar-Carreno, a professor of virology in Cornell's College of Veterinary Medicine, and Neha Kamat, an associate professor of biomedical engineering at Northwestern University, initiated this project during the COVID-19 pandemic. They recognized the urgent need for faster vaccine development methodologies in light of emerging infectious diseases. "We were fortunate that prior research on coronaviruses provided insights into effective antigens for COVID-19 vaccines," Kamat stated. "However, for future epidemics involving less-known viruses, rapid assembly and screening of vaccine formulations will be critical."

The innovative method produces and folds full-length viral membrane proteins directly into synthetic lipid bubbles known as liposomes, enabling the creation of vaccine candidates in a matter of hours rather than the traditional weeks or months. This rapid production capability could prove essential in global vaccine distribution, particularly in regions with limited infrastructure and refrigeration.

The research demonstrates that by eliminating the need for live cells in vaccine production, the complexity and time associated with traditional vaccine development are significantly reduced. Cell-free protein synthesis systems utilize the molecular machinery of cells but operate in vitro, allowing for expedited protein expression. The system successfully produces membrane proteins capable of integrating themselves into lipid vesicles without the aid of protein chaperones, which are typically necessary in living cells.

Daniel remarked, "By removing the reliance on living cells, we can manufacture vaccines under simpler conditions, translating to much faster production times."

The liposomes created by the research team closely resemble the structure of the Nipah virus, displaying critical proteins on their surface to enhance the immune system's recognition and response to potential infections. The study incorporated two essential Nipah proteins, NiV F and NiV G, which play crucial roles in the virus's ability to fuse with and attach to host cells, respectively. Adjustments to the liposome components, including the types of fats used, contributed to improved protein production and insertion, resulting in a more robust immune response.

Additionally, lipid A, an ingredient known to enhance immune response, was included in the liposome formulation. Mice administered liposomes containing both viral proteins and lipid A exhibited higher antibody production compared to those receiving simpler versions. Among the proteins tested, NiV G elicited a stronger immune response, establishing its prominence in the formulation.

The research was not only groundbreaking in its methodology but also in its implications for future vaccine strategies. "The beauty of this system is its tailorability, allowing us to create vaccine particles optimized for peak performance while identifying which components contribute most to that success," Daniel explained.

As the World Health Organization classifies Nipah as a virus with pandemic potential, the implications of this research are far-reaching. The ability to quickly develop adaptable vaccines could transform public health responses to emerging viral threats. Moreover, the platform's versatility suggests its applicability to a wide range of viral challenges and even therapeutic vaccines for cancer.

The project received support from the National Science Foundation, the McCormick Research Catalyst Program, and the National Institutes of Health, underscoring the importance of collaborative research efforts in advancing vaccine technologies for public health.