Virus Vaccines Assembled in Hours With New Cell-Free Method

Breakthrough mimics viral structure for rapid pandemic response

Scientists have engineered a revolutionary cell-free system capable of constructing nanoparticle vaccines that precisely mirror viruses at a molecular level. This groundbreaking advancement promises to dramatically accelerate our ability to combat emerging pandemics.

Speeding Vaccine Development for Deadly Threats

Researchers from Cornell and Northwestern universities have created a swift, cell-free process for building nanoparticle vaccines. This technique meticulously reproduces viruses’ molecular architecture, offering a potent new strategy for swift responses to widespread infectious diseases.

By synthesizing and properly folding full-length viral membrane proteins directly within synthetic lipid spheres known as liposomes, the method produces vaccine candidates in mere hours. This contrasts sharply with the weeks or months typically required for traditional methods and could usher in faster, more adaptable immunization strategies against lethal viruses like Nipah.

A Platform for Future Health Crises

The research, detailed in the journal ACS Nano, specifically examines the Nipah virus. This pathogen causes severe neurological and respiratory illness, boasting a fatality rate as high as 75%, with no existing approved treatments or vaccines. Consequently, the World Health Organization designates Nipah as a virus with significant pandemic potential.

“We need ways to rapidly assemble and screen vaccine formulations that present the most effective proteins for a given virus,” stated **Neha Kamat**, associate professor at Northwestern University. The team initiated their vaccine development during the COVID-19 pandemic, recognizing the critical need for accelerated vaccine creation processes.

This innovative platform extends beyond Nipah virus. Its adaptability allows for application against a wide array of viral threats, and even therapeutic vaccines for cancer. The system’s inherent simplicity and speed are particularly advantageous for global vaccine accessibility, especially in regions with limited refrigeration and less developed infrastructure.

Eliminating Cellular Constraints for Faster Production

The novel approach facilitates the rapid production of vaccine components without the use of living cells. This bypasses the time and complexity typically associated with conventional vaccine development. Cell-free protein synthesis systems harness cellular machinery in vitro, enabling protein expression within a few hours.

This system generates membrane proteins that can self-fold and integrate into lipid vesicles, obviating the need for protein chaperones essential within living cells. “By eliminating the need for living cells to produce these vaccine particles, we are no longer constrained by the specific conditions that are needed to maintain those living cells,” explained **Susan Daniel**, William C. Hooey Director at Cornell. “That means we can manufacture these vaccines in simpler conditions and that translates to much faster production times.”

Mimicking Viral Structure with Tailored Components

The team’s technique fabricates minute, fat-based spheres called liposomes designed to replicate the structural characteristics of actual viruses. These liposomes display crucial Nipah virus proteins on their surfaces, aiding the immune system in identifying and counteracting potential infections. The researchers incorporated two key Nipah proteins, NiV F and NiV G, into the liposomes. NiV F facilitates viral entry into host cells, while NiV G aids in attachment.

To optimize protein production and insertion, a specific segment of NiV F, which normally guides the protein to its cellular destination but is unnecessary outside of cells, was removed. Adjustments were also made to the liposome’s lipid composition, including ingredients like phosphatidylethanolamine and phosphatidylserine, which enhanced membrane flexibility and improved protein integration, leading to a more robust immune response.

Boosting Immune Response with Key Additives

The researchers further enhanced the liposome formulation by adding lipid A, a known immune stimulant. Mice vaccinated with liposomes containing both viral proteins and lipid A generated a stronger antibody response compared to those receiving simpler formulations. Between the two tested proteins, NiV G proved to be the more potent antigen, eliciting a stronger immune reaction.

“The beauty of this system and formulation approach is that we can create vaccine particles tailored with specific components that allow us to test the impact of each component on the immune response,” commented **Susan Daniel**. “This tailorability means we can produce vaccine particles optimized for the best performance while learning what components contribute to that success.”

This scientific advancement arrives at a critical time. According to the World Health Organization, nearly 75% of emerging infectious disease outbreaks between 2014 and 2022 were zoonotic, originating in animals (WHO, 2023), highlighting the urgent need for rapid response tools.